| 00:00 | Okay, welcome back. This is , cellular neuroscience lecture too. And |
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| 00:09 | finished last lecture by briefly reviewing the and why what I explained to you |
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| 00:18 | the slide. As today we're gonna about neurons and glia and start understanding |
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| 00:25 | functions and different subtypes. But one that I mentioned is that there are |
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| 00:30 | neurons that express neurotransmitters which was sanitary, neurotransmitter, gaba inhibitor neurotransmitter |
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| 00:37 | are widely distributed throughout the brain. so much a widely distributed throughout the |
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| 00:43 | , you'll find them in the brain and the cerebellum and the spinal cord |
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| 00:47 | the cerebrum. And these are what consider amino acid neurotransmitters. However, |
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| 00:54 | are other ways of chemical communication and brain and those are what we call |
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| 01:01 | modulators. And those neuro modulators such acetylcholine, such as norepinephrine, such |
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| 01:10 | serotonin. They expressed by a very subset of cells that we typically refer |
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| 01:17 | as nucleus nucleus by definition is a of the cells responsible for the same |
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| 01:23 | very similar function processing the same single in this case expressing a specific specific |
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| 01:33 | with very locally in this nucleus and the external projections that will essentially release |
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| 01:39 | neurotransmitter broadly throughout the brain. So is where we ended last last week |
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| 01:52 | today we're gonna move into this material be for the next three lectures when |
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| 02:02 | talk about neurons and glia And neurons about 10% of the total cell mass |
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| 02:12 | population if you, may. It's fine without cutting anything off and 90% |
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| 02:34 | the south will be glia. The 90%. So most of the neuroscience |
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| 02:39 | always say has focused mostly on neuron and only the last couple of decades |
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| 02:45 | seen an increase in studies on It is because glia have been thought |
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| 02:49 | a long time as passive in the of not contributing much to the active |
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| 02:55 | or processing of that activity in your . And we're finding out that that |
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| 03:00 | not be the case that we are fact, as we mentioned last time |
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| 03:04 | a part of the tripartite synapse and influence synaptic transmission and neuronal communication. |
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| 03:12 | it is operating at slower temporal scales neurons are very fast and they communicate |
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| 03:19 | each other within milliseconds. Uh Glia take tens of milliseconds, hundreds of |
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| 03:26 | to have their way of communication sometimes longer because certain types of we are |
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| 03:32 | in regulating inflammatory processes in the neurons then can be described like chips |
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| 03:40 | a chocolate chip cookie glia is like but it's not passive again without leah |
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| 03:47 | wouldn't exist, wouldn't survive and be to migrate and have the installation. |
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| 03:52 | need the nutrients and the protection they from Julia as well as the active |
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| 03:57 | of these neurotransmitters, neurons in the are roughly divided into excitatory and inhibitory |
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| 04:08 | neurons will be expressing glutamate and releasing that glutamate will typically have an excitatory |
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| 04:16 | on the pasta Matic neuron that will to excite that pasta, Matic neurons |
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| 04:21 | inhibitory neurons they express and release gamma you know butyric acid or Gaba. |
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| 04:28 | if you were to stain the brain would see a lot of excited to |
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| 04:33 | lot of inhibitory neurons that would stain for blue domain or that would stain |
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| 04:39 | for Gava or an enzyme that regulates called God these are amino acid |
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| 04:48 | They are responsible for fast neural As I mentioned last time when you |
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| 04:54 | of glutamate and Gaba you can think plus and minus or switched on excitation |
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| 05:00 | off inhibition all of these other chemicals we described like serotonin, norepinephrine and |
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| 05:07 | add a lot of color, a of control to that on and off |
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| 05:12 | . You can have if you have analogy with lights and dimming switch different |
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| 05:16 | , turn on and off, different of the room eliminated differently. And |
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| 05:20 | what these other non amino acid neurotransmitters to the general communication in the |
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| 05:28 | Now there are ion a tropic and tropic receptors that we'll discuss when we |
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| 05:35 | to the um cell membrane. Talking cell membrane but in general uh in |
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| 05:43 | cell number and when we talk about and protium channels and some of them |
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| 05:50 | receptor channels and others are receptors but channels. We will have to distinguish |
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| 05:55 | different ways in which these channels can activated. Okay, so we will |
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| 06:01 | today a little bit about the types channels of ion channels. And this |
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| 06:09 | very important because this is how the happens between neurons and this is how |
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| 06:16 | flux of ions happens within neurons in out of neurons and generating the fast |
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| 06:22 | als for neuronal communication. So if look now in much greater detail, |
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| 06:31 | simple way of describing the brain neuronal and excited to an inhibitory is simple |
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| 06:38 | some of them also will have serotonin others will have that. We talked |
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| 06:45 | these nuclei right? And it's also it's just not one subtype of excited |
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| 06:52 | , not one subtype of inhibitory And there are overall maybe 150 subtypes |
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| 07:00 | different neurons. The variety of glial is not as abundant as their |
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| 07:09 | And so in variety there are illegal sides that are shown here and as |
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| 07:16 | can see a legal de emphasize will around their processes and create myelin ation |
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| 07:24 | insulation to neuronal axons. And this is really important because if you want |
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| 07:31 | conduct electricity through a wire, you wires that are insulated. So are |
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| 07:38 | neuronal axons are insulated so that they electricity to the particular specific locations and |
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| 07:46 | over long distances without losing the charge without losing the current a little dangerous |
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| 07:54 | . Each foot or beleaguered underside will a single axonal segment on neuronal |
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| 08:03 | Astra sides. A very important some of real cells that will talk about |
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| 08:10 | more than other subtypes of real And astra sides is illustrated here. |
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| 08:16 | can see that they're actively involved in the activity in neuronal processes in particular |
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| 08:24 | the synapses that are happening there. third part in the tripartite synapse that |
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| 08:30 | talked about. Astra sides decides controlling synoptic transmission also regulate and um buffer |
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| 08:43 | increases in ion concentrations, abnormal increases chemicals. And they also have a |
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| 08:50 | of transporting glutamate uh and working and synthesizing that glutamate and glutamine before giving |
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| 08:58 | back to the excitatory neurons. Astrocytes have their end feed these processes here |
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| 09:06 | the capillaries and these are the blood of the micro capillaries that are innovating |
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| 09:12 | brain tissue throughout. And astrocytes are of what is called the blood brain |
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| 09:18 | . So these glial cells will be policing and controlling what substances get in |
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| 09:26 | the blood into the brain and potentially other way around there's a tight control |
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| 09:32 | not everything that's in the blood gets the brain. Very small molecules, |
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| 09:38 | soluble molecules. They will be able cross the blood brain barrier and get |
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| 09:44 | the astra sides. Cross the astrocytes into the brain tissue molecules that have |
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| 09:50 | transporters, facilitators that can carry them the blood brain barrier will get into |
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| 09:56 | brain tissue. But otherwise there's going be a pretty significant barrier or filter |
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| 10:06 | you may that determines what stays in blood and what crosses into the brain |
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| 10:13 | smallest and the fastest and the most glial element in the brain of micro |
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| 10:19 | cells, they're involved in injury So if there is an injury locally |
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| 10:26 | the brain tissue, micro glial cells mobilize their processes and will direct their |
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| 10:32 | toward the side of the injury and will also physically start migrating through brain |
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| 10:38 | toward the side of the injury. glial cells will be concerned with the |
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| 10:44 | of pro inflammatory molecules that we call . So michael glial cells says, |
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| 10:51 | inflammatory immune response in the brain, would be activated if there is injury |
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| 10:57 | the brain, they would be activated there is an infection in the |
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| 11:01 | And very much again, on a a slower tempo scale, we're now |
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| 11:09 | about minutes to hours for microbial cells activate their processes to extend them to |
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| 11:16 | migrating and controlling the amount and release the cytokines for the proper activation of |
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| 11:22 | immune response. So you have the spinal fluid here in cerebrospinal fluid is |
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| 11:32 | in the ventricles that is circulated throughout brain and enters into interstitial spaces as |
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| 11:40 | . But the extra cellular fluid that seeing here is different from the intracellular |
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| 11:46 | that is going to be found inside south in general. The inside and |
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| 11:51 | of the South are water like they're saline water like environments. Especially |
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| 11:57 | outside of the Southwest. Salty is in sodium chloride. The inside is |
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| 12:02 | a little bit more bitter. It's with potassium mines. But both of |
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| 12:09 | extra cellular environment and inter cellular environment Aquarius solutions. Now there's many different |
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| 12:16 | by which we can classify neurons. of all neurons come in different shapes |
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| 12:22 | sizes. So we can uh we sub classify them and classify them based |
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| 12:31 | their anatomy or morphology of how these actually appear. Some of them will |
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| 12:37 | dendrites, multipolar selves, Others will two axons, a peripheral and the |
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| 12:45 | axon and no damn dried. So can distinguish different cell subtypes based on |
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| 12:51 | morphology. We also can distinguish them on their projections or connectivity. Certain |
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| 13:02 | will remain local within the network and cells that remain local within the network |
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| 13:11 | refer to as into neurons and they interconnect with other excitatory cells and |
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| 13:18 | Sir, typically inhibitory and excitatory cells as pyramidal cell, an example of |
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| 13:25 | excitatory cells. Excitatory and these inter can talk to each other so inhibitory |
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| 13:32 | inhibitory interneuron can talk to another inhibitory and they can talk to another excitatory |
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| 13:42 | and these inhibitory neurons will release Gaba the excitatory neurons will release glutamate. |
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| 13:52 | the inhibitory neurons versus excitatory neurons. versus glutamine. Now these inter neurons |
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| 14:02 | actually going to exert their activity locally a certain neuronal network. That means |
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| 14:11 | their projections are going to be short projections around it. All cells that |
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| 14:17 | typically excitatory will actually have long And those projections will come outside of |
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| 14:25 | local neuronal networks and will interconnect to nerve neuronal structures. So we can |
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| 14:35 | neurons based on their connectivity, whether are projection cells or whether they're inter |
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| 14:43 | . And just by virtue most of inter neurons are inhibitory and most overwhelming |
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| 14:51 | of the projection cells are excitatory So this is another way of classifying |
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| 14:59 | , excited versus inhibitory. Different cells also express different subset of genes. |
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| 15:08 | when I said that there's 150 potentially subtypes of neurons. That's because they |
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| 15:15 | have a slight different expression of the channels chemicals some of them will |
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| 15:23 | their opponent, others will express a gaba glutamate, this is all |
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| 15:27 | variety. And these, what we ourselves specific markers. But we'll get |
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| 15:33 | that in a second. Uh Finally produce action potentials. These are very |
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| 15:42 | large amplitude fluctuations, large amplitude for south. There are approximately 100 mil |
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| 15:49 | all fluctuations in over a matter of or two milliseconds and these different some |
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| 15:57 | of neurons by having different anatomy expression molecules within themselves, expression of ion |
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| 16:08 | . They will also have their own firing properties or firing patterns as we |
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| 16:15 | it. Mhm. This is the published action potential from Hodgkin and |
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| 16:24 | It was recorded in the late And we really just discovered and were |
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| 16:31 | to capture and record these action potentials the late 30s, mid 40s and |
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| 16:35 | 50s. So based on the previous of the history when ramon alcohol was |
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| 16:43 | those beautiful drawings reconstructions of the south camera lucida uh He did not know |
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| 16:51 | the cells neurons can produce action He knew that they can conduct electricity |
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| 16:59 | they can generate and conduct electricity. didn't know because there were no tools |
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| 17:06 | enough to pick up action potentials and neurons. Most neurons have four functional |
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| 17:16 | despite their differences, they will have infant region. So one neuron contacting |
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| 17:23 | neuron, there's a sensory neuron which be picking up information from the |
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| 17:28 | joints or muscles, motor neuron communicating another neuron. Local inter neurons projection |
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| 17:37 | neurons. So yes, there are projection into neurons and nora neuroendocrine |
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| 17:45 | You have integrated region which is typically selma of these neurons. You have |
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| 17:50 | conduct I'll region which is the So the receptive region of the input |
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| 17:55 | is typically dendrites or selma's, the . I'll aspect of neurons is axon |
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| 18:02 | electricity and the output is the external . The output in this case is |
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| 18:08 | the form of chemical release neurotransmitter release that release can happen on to another |
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| 18:17 | onto a muscle even on a capillary or in more general terms in the |
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| 18:24 | the uh systematic circulation. As a with a neuro endocrine system and neuroendocrine |
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| 18:34 | which will actually influence the overall systematic influenced hormone release. Yeah. So |
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| 18:43 | and projection to neuron. Is that it's the difference of the neuronal |
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| 18:47 | Um but it was still probably like sale but it was just. |
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| 18:52 | Yes. But it's also an exception every science and in neuroscience are always |
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| 18:59 | . So when we say that excited of projection while there are some in |
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| 19:03 | neurons that are projection cells. So say that gaba cells are all inter |
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| 19:08 | that are localized. There's actually some very cells that are localized overwhelmingly. |
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| 19:15 | is that these are the rules by we understand the brain. Good |
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| 19:24 | So morphology you can see that some the salsa unit polar, they're all |
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| 19:31 | to the same poll dendrite and axon looking off cell bodies at the |
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| 19:35 | Some of them are bipolar which is cells of retina. Others of pseudo |
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| 19:42 | sudo. You know polar cells are neurons that travel and carry the information |
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| 19:47 | the spinal cord proper. Then you multipolar cells you have an example of |
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| 19:54 | motor neuron which is multi polar parameter in the middle which looks like pyramid |
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| 20:01 | is multi power. And on the you have a poor Kinji cell which |
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| 20:06 | this massive, massive sell the massive branches of the cell that you |
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| 20:15 | find in Sarah Bella and it can up to 150,000 synapses. And so |
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| 20:23 | of the synopsis will be made on dendrites and dendritic spines on the soma's |
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| 20:29 | these cells. And some other cells spinal motor neuron can have only or |
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| 20:35 | have typically only up to 10,000 Despite the difference 210,050. There's still |
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| 20:46 | pretty complex computational task. Out of 10,000 synapses, 80% could be excitatory |
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| 20:56 | . Uh 10 - 20% could be analysis. So the processing and the |
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| 21:05 | that neurons have to make is still of thousands of excited to inhibitors. |
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| 21:10 | active at the same time. Plus neuro modulator chemicals that are active and |
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| 21:17 | the activity in in in that particular whether it's going to produce an action |
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| 21:22 | and communicate that information or be quiescent a while. So when we put |
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| 21:28 | of this together, I'll remind you in your lecture notes, if you |
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| 21:36 | to the content to the class content this is information that I'm actually supposed |
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| 21:46 | share with you this case. We're about all of these different subtypes of |
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| 21:56 | that we discuss? All of the subtypes of inhibitory cells and solitary cells |
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| 22:02 | how do we distinguish between them? can we tell the difference? I |
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| 22:08 | there's 150 different types of neurons. then I said well there's some |
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| 22:13 | some norepinephrine, some colon glutamate But that's only a handful. That's |
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| 22:22 | 150. So how come there is 150 or more subtypes of neurons and |
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| 22:29 | is this variety of diversity stemming And we use this circuit as an |
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| 22:37 | that illustrates some of what we call circuits. Some of the canonical rules |
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| 22:46 | which these circuits in the brain communicate structure that we're looking at in particular |
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| 22:53 | a part of the hippocampus. For in the brain is responsible for semantic |
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| 23:03 | , semantic memory. Is facts. , events, history, stories. |
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| 23:14 | this is the kind of memory that processes in codes and recalls semantic |
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| 23:24 | The hippocampus is also involved in emotional processing. The campus is predominantly a |
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| 23:33 | layer structure that has stratum ready item top stratum and stratum orients and if |
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| 23:44 | looked and we did a stain in . And this is a part of |
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| 23:50 | . A one area which stands for ceremony area one or demons horn area |
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| 23:59 | C. A one and there are areas in hippocampus is this is just |
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| 24:04 | area of the structure in the brain the hippocampus. If we were to |
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| 24:10 | glutamate stain Gabba stain and take this of hippocampus and stay in all of |
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| 24:18 | excitatory cells that have glutamate all of inhibitory cells that have gabba We would |
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| 24:25 | out that about 80-90 of cells in circuit. And actually because this is |
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| 24:35 | circuit, this will be also applicable neocortex. For example hippocampus is a |
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| 24:42 | layer construction is referred to as our cortex because it's three layered structure arcade |
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| 24:48 | but the same principle would also apply the new cortex or the neocortex which |
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| 24:55 | our cerebral cortex. Also 80-90% of of the cells. And the circuit |
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| 25:01 | be excitatory cells and 10 to 20 be inhibiting ourselves. So the brain |
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| 25:15 | the cortical centers and the hippocampal centers by the abundance of the excitatory cells |
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| 25:24 | numbers. How about the variety and do we get to that variety? |
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| 25:32 | , one of the most canonical Again, it's canonical because it reappears |
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| 25:41 | different places in the brain is the cells, parameter cell has the demo |
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| 25:49 | , it has the axon it has dendrites at the base of the |
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| 25:54 | it has a pickle den rides at apex. Okay. And this is |
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| 26:02 | base and this is the axon an would be violin ated with a violent |
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| 26:10 | throughout and this is the external terminal this is where the neurotransmitter release |
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| 26:20 | So we have this parameter cells and parameter cells are excitatory projection songs. |
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| 26:29 | in Hippocampus overwhelming majority of them, , of these 80 90% of phenomenal |
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| 26:37 | will be located in stratum from the . In this wide strip you can |
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| 26:43 | this white layer strip layer. The layer stratum stands for layer from the |
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| 26:50 | stands for criminal. It's called so it's overwhelmingly populated by the soma or |
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| 26:57 | bodies of the criminal cells. So camerata above you have stratum radiate um |
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| 27:05 | the radio bottom layer below you have orients or the orient slayer. This |
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| 27:12 | just one piece of hippocampus. One C A 13 dominant layers dominant cells |
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| 27:21 | number excitatory cells. Most of them living in the strip layers stratum berman |
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| 27:28 | . They will be releasing glutamate so sauce or make releasing sauce and they |
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| 27:39 | about the same. These are the cells that you're seeing here parameter |
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| 27:45 | So this parameter cell looks the same this parameter sell this parameter cell looks |
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| 27:50 | same as two other parameter cells. not much difference in morphology. You |
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| 27:55 | say that maybe the one in stratum adam looks like it would have a |
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| 27:59 | of them drive saying okay but then will find some cells that have so |
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| 28:05 | stratum criminality that will also have a bit shorter. Done rise to say |
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| 28:09 | you really they look the same. morphological e if you were to take |
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| 28:15 | criminal cell subtype that is shown here lighter color to darker color. You |
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| 28:22 | not be able to distinguish them So the only way that you would |
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| 28:28 | able to distinguish them will say you what they don't they? They there |
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| 28:33 | three layers so they live in three layers. Okay, chuck moore. |
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| 28:38 | importance of where things are located the architecture. But this this sample the |
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| 28:44 | thing is what do they express and cells will express certain molecules. They |
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| 28:51 | express calcium binding programs. In this it's cal dependent or C. |
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| 28:57 | Which is a calcium binding protium. some parameter cells will be positive for |
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| 29:03 | din Din and others will be So they look the same. The |
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| 29:09 | is they live in three different layers some of them are called indian |
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| 29:15 | Some of them are negative. The that are in the layers seem to |
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| 29:17 | in for a middle layer seem to dominated by being positive by kelvin. |
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| 29:23 | that's the difference in three subtypes of sets. So this is somewhat uh |
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| 29:33 | . There is not that much variety in the excitatory cells but it also |
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| 29:39 | demonstrates that these excitatory cells will send axons or projection axons and these axons |
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| 29:46 | actually go outside of areas they want go outside of the hippocampus. So |
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| 29:53 | projection south long range that will come and interconnect with another adjacent area of |
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| 30:00 | hippocampus. Or the cortex against original which is close to the hippocampus. |
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| 30:07 | now you're also seeing on this diagram 1, 23 all the way through |
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| 30:18 | and you're seeing cells that are shaped and now you're seeing a variety of |
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| 30:25 | . So what is this? 21 for All of these 21 subtypes of |
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| 30:33 | will stain for Gaba or God is enzyme that synthesizes Gaba. So now |
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| 30:42 | looking at the inhibitory neurons, their , they will synthesize Gaba and God |
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| 30:53 | an enzyme that makes Gaba. So you were again to look at this |
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| 31:04 | subtypes of cells, whether they say , you can look at 19 or |
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| 31:09 | it doesn't matter, they all be for God and gobble. But if |
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| 31:17 | do a stain like a Golgi we talked about how Golgi stain will |
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| 31:26 | the morphology, precise morphology. And can see that there is not much |
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| 31:32 | in morphology and parameter cells. But you look at this 21 different subtypes |
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| 31:36 | cells you see that some of them dendrites that are pointing vertically. Others |
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| 31:43 | dendrites that are pointing horizontally. Others dendrites that are kind of a split |
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| 31:52 | pointing also vertical directions. And finally yellow cups are the synopses. So |
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| 32:01 | is the location of the synapses where inhibitory cells where these inhibit their cells |
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| 32:08 | going to synapse onto the excited very some of them will synapse at the |
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| 32:15 | . But a lot of them will inhibitory projections will be located very close |
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| 32:25 | the soma. Soma is the decision region, the integrated region which will |
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| 32:30 | a lot of negative projections right around soma which has very strong influence and |
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| 32:37 | activity in these excited to ourselves. these as you can see some of |
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| 32:44 | yellow cups are the synapses that will a pickle dendrites. Some of these |
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| 32:50 | cups like in number two and number will target the paris, somatic regions |
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| 32:56 | the excitatory cells. The closer you to selma, the more influence you |
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| 33:02 | of what that cell is going to because Selma integrates information from these 10,000 |
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| 33:11 | and acts on initial segment is where action potential is generated. So the |
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| 33:17 | you are to influencing the integration and of action potential, the stronger influence |
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| 33:25 | have of what this other cell in case excited to sell is going to |
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| 33:30 | . But as you can see some the synopsis on the selma, some |
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| 33:35 | them are optical, some of them the basal dendrites. That's already a |
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| 33:40 | difference. So we can tell by of the dendrites location of the synopsis |
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| 33:47 | of the soma. So that already us a clue we're looking at potentially |
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| 33:51 | subtypes of inhibitory cells. Then you to this point where you're looking at |
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| 33:57 | number two and number four. And you look at the morphology of these |
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| 34:04 | cells, they look the same. have rounder. So hmas that are |
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| 34:09 | in pyramidal layer, they have dendrite here that are projecting vertically and they |
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| 34:19 | all of their axons. Number Number four targeting the same region of |
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| 34:24 | cells then you ask a question. are these two different subtypes of cells |
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| 34:29 | not? And if they are how you distinguish these two different subtypes of |
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| 34:34 | ? And the answer is that you to stain them for these cells specific |
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| 34:39 | . Just like we talked about cal in certain parameter cells express Calvin din |
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| 34:45 | others do not which makes them to subtypes of parameter cells. The same |
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| 34:50 | these number two and number four inhibitory cells. Number two will be a |
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| 34:58 | cell we call it a basket cell it's really cool. It's axons looks |
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| 35:03 | a basket that wrap around the parameter cells. And number four is the |
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| 35:09 | CCK cell. So number two is volume and positive that will express this |
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| 35:15 | per volume in or PV and number will express CCK which is called the |
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| 35:22 | kind and and potentially another marker such v glued three and you can get |
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| 35:28 | more and more and more markers is more differences. So now you have |
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| 35:34 | the slides first of all with glutamate Gaba you saw that there's a lot |
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| 35:39 | glutamate cells not much variety in the cells that send the information out and |
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| 35:46 | lot of variety in the inhibitory cell . So most of the variety than |
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| 35:53 | this neuronal subtypes in the cortex. because its canonical will be the same |
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| 35:59 | the hippocampus, in the hippo capital , three legged cortex and neocortex six |
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| 36:04 | cortex. You have abundance and variety inhibitory cells over the excitatory cells. |
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| 36:14 | this is it's no there's lesser there's 10 to 20% of those inhibitor into |
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| 36:24 | . But they come in many more . And the final thing to mention |
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| 36:31 | their activity will stay local. They influence parameter solid excited to sell locally |
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| 36:38 | the C. A. One. will not project out of the |
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| 36:40 | One. So there's a lot of in how they can influence the excitatory |
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| 36:49 | cells that are going to communicate and that information out of the sea a |
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| 36:54 | region. So it's a lesser number variety. And if you have a |
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| 37:02 | variety in anything life is more Um So if you just had two |
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| 37:09 | that would be boring, you know . But if you can have a |
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| 37:15 | of flavors and you know this is variety of internet as a processing in |
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| 37:20 | brain becomes more complex that it allows to have more complex processing. But |
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| 37:26 | is just looking, we haven't gotten the activity yet. We're just looking |
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| 37:31 | cider architecture where the cells are We're looking at their morphology. We're |
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| 37:36 | at whether they're excited or inhibitory we're at their synaptic connectivity, the projection |
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| 37:44 | and whether they have a specific marker not. But because they're different cells |
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| 37:50 | because they actually have different channels that express, they can produce different patterns |
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| 37:58 | action potentials. So this is now Neocortex. Neocortex is a six layered |
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| 38:04 | and if one were to record from variety of adjacent cells that would first |
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| 38:09 | all find out that most of these that have unique patterns or what we |
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| 38:17 | this is a stuttering pattern. This delayed firing, this is bursting |
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| 38:23 | These unusual patterns are typically the inhibitor neurons and it's coming from the inhibitor |
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| 38:32 | neurons. Whereas the classical parameter this is a classical accommodating pattern from |
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| 38:39 | parameter cell, it's right here and three subtypes of parameter cells will have |
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| 38:46 | same pattern of action potential firing. classical accommodating pattern of action potential |
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| 38:53 | But the diversity in the firing patterns action potentials comes from the inhibitory into |
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| 39:01 | in the hippocampus in neocortex and in , so it's as if excitatory cells |
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| 39:08 | a very robust code, I'm on I need to communicate it to somebody |
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| 39:14 | but the inhibitory cells have the ability modulate the output of that code and |
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| 39:22 | it's given out to the adjacent brain because inhibitory synapses if there's a lot |
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| 39:29 | inhibition it will actually hyper polarize this will quench activity in this neuron will |
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| 39:36 | allow for this neuron to fire an potential and project information out. |
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| 39:45 | So these are examples of recordings that show in my other course and some |
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| 39:51 | the slides are also from my other . That's because they're not in the |
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| 40:00 | there in my notebook and there in papers. This is some of my |
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| 40:05 | that I've done at George Mason University a post doc and later at the |
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| 40:12 | of Houston here. I'm sorry about . So what we have is first |
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| 40:18 | all this image here, it shows we have neurons that we can |
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| 40:25 | We use the infrared microscopy technique to brain slices. We put these slices |
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| 40:31 | a microscope, we have the environment these brain slices that resemble environment of |
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| 40:36 | brain. So we try to fool as if they're still part of the |
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| 40:40 | , they're viable and respond. They action potentials activity for hours If they're |
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| 40:46 | in the correct environment with artificial cerebrospinal as well as oxygen. Um you |
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| 40:54 | see that we can place these slices individual neurons and direct micro electrodes. |
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| 41:02 | a typically bora silicate micro electrodes that have inter cellular solution inside of them |
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| 41:08 | supposed to match this electorate solution is to match the inter cellular solution of |
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| 41:13 | cells and we can patch onto these . It's called patch clamp technique. |
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| 41:19 | talk about it in a little bit we can basically stimulate these student neurons |
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| 41:25 | these micro electorates and record their responses the form of that membrane potential |
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| 41:31 | And in the form of the action firing patterns. And these two neurons |
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| 41:37 | get the same input. And the on the left here produces a very |
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| 41:44 | firing frequency of action potentials. And neuron on the right it receives the |
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| 41:49 | same input electrical input through the same of electrode micro electrode. And instead |
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| 41:56 | produces this what we call a classical or parameter like cell firing pattern. |
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| 42:08 | so during the experiment inside these electrodes have a die in the older versions |
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| 42:15 | was used to be called biocyte in called neuro biotin. Now. So |
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| 42:22 | the experiment as you're recording activity from two cells that die leaks inside these |
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| 42:29 | cells and you do that for a . So after you finish the experiment |
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| 42:37 | have to prove the reviewers what cell did you record from in the |
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| 42:47 | one of them fired you know and like manner here another one fired a |
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| 42:54 | fast frequency like that of action Which one which which subject is exactly |
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| 43:02 | you looking at? So the dye enters into the cells during the experiment |
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| 43:09 | can take the slice after the experiment put it through um you know history |
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| 43:15 | and you will reveal without die the morphology and the location of yourself on |
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| 43:22 | slice. So you can see here this is S. R. Which |
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| 43:26 | for stratum ready atom of that parameter piece. This is stratum pyramidal of |
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| 43:34 | parameter layer. This is stratum So after I finished the experiment I |
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| 43:43 | through um you know history chemistry but not enough to know morphology. |
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| 43:48 | Because we said if you want the answer sometimes the cells will look the |
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| 43:54 | . Exactly will fire maybe even the . And they do in fact have |
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| 43:59 | same external projections. So how do know which one? So finally we |
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| 44:04 | to make sure we use immune artistic and we use antibodies. So we |
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| 44:10 | them for PV. Which is part albumin. We stand them for some |
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| 44:13 | a statin we stained them for B. Which stands for neuro |
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| 44:19 | So you can do multiple marker stain these slices to make sure that all |
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| 44:26 | this work that you have done with . This is typically wrote them slices |
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| 44:32 | the slice is under microscope all of work that you did to get to |
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| 44:35 | experiment show something that you can answer question to. The reviewers. So |
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| 44:42 | a biotin will allow you to reconstruct precise morphology of the cells and their |
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| 44:48 | in the network. You know which it is. You know what the |
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| 44:52 | look like. You know what the look like. And the one on |
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| 44:55 | right looks like parameter cell and the on the left does not look like |
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| 45:00 | parameter cell. So because it doesn't like a parameter cell and I targeted |
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| 45:08 | non prom it'll sell in that particular . I actually targeted cells that are |
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| 45:13 | for some odd A statin and that called number seven here all L. |
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| 45:21 | . Cells that stands for orients la elam cell is number seven. It |
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| 45:31 | its axon travel all the way from orients layer to this fourth layer which |
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| 45:38 | didn't tell you about which is So it has this very very long |
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| 45:47 | that projects out and targets the optical of these parameter cells. And I |
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| 45:55 | thought that when I look at these they look oblong and I always thought |
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| 46:00 | I just had a kind of an for for these cells and the network |
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| 46:06 | pick them off. And so I quite a bit of work in describing |
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| 46:10 | electrical interactions between all alarm cells and cells in particular during seizure like |
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| 46:18 | When neurons start generating seizure like So we looked at a lot of |
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| 46:23 | and so surely enough, this is semantic statin positive alarm cell on the |
|
| 46:30 | , on the right. You have the right, you have a parameter |
|
| 46:35 | and the reviewers except the paper. really interesting paper to representation of this |
|
| 46:52 | here. The one is on its morphology and when you do the fluorescent |
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| 46:58 | , then you just typically detect the . You don't go for higher resolution |
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| 47:03 | you want to make sure that the like alarm style that I reported from |
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| 47:07 | it is and I filled with no . I want to make sure that |
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| 47:12 | cell is gonna stay positive for no . So I know it's my cell |
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| 47:16 | all the others around they don't get . Only the ones that get the |
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| 47:21 | is um started and then get So I know that's my cell right |
|
| 47:25 | . I'm going to use a second since I know this is my neural |
|
| 47:29 | sell and what is going to be second market. And in this case |
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| 47:33 | been on some kind of staggered which S. O. N. And |
|
| 47:37 | was some kind of sacrifice and because located in this life and because it |
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| 47:41 | this that it matches up to other work and to the diagrams that we're |
|
| 47:47 | previously for us to say definitively it all around south. Okay. How |
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| 48:00 | of the electrode electrode, you actually you don't leak out anything. Um |
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| 48:12 | that when you patch your cell. , let me take it back a |
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| 48:16 | bit as you're approaching yourself a patch with micro electrode. I said you |
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| 48:21 | look out, you leak out a small amount of that die. But |
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| 48:26 | guy doesn't get picked up extra cellular well by the surrounding neurons. So |
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| 48:32 | the neuron that gets patched and you on top of patching you sometimes have |
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| 48:38 | pulsate the positive and negative current because the movement of ions inside and outside |
|
| 48:45 | electric and it will actually propel the . Were saying when you finish the |
|
| 48:51 | , like I measured the action potential seizure activity. If I have the |
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| 48:56 | say make sure you fill it And that means that I was gonna |
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| 49:01 | stepwise currents, electrical currents positive and to just move things in and out |
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| 49:06 | the electrode into the south. And when it's completely filled and that's when |
|
| 49:11 | reveal really good and morphology And sometimes know, and sometimes you you don't |
|
| 49:18 | this lucky and sometimes you know out 20 cells you record and failure reconstruct |
|
| 49:25 | and artists you're just not lucky, something didn't exposed died in. It |
|
| 49:31 | look the slides bent over and now not sure like the cell is bent |
|
| 49:37 | and you have to realize it's a it's a bit of a, you |
|
| 49:41 | , it's a skill and an art then you have to reconstruct them. |
|
| 49:45 | to reconstruct them ramon, alcohol. to use this uh microscope with a |
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| 49:52 | set tube to do the reconstructions of called camera lucida. And now you |
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| 49:59 | project this image onto the computer from microscope and you trace around it and |
|
| 50:07 | is a certain level of automation in lucida. But it's not perfect. |
|
| 50:15 | means that there's still a human element tracing these neurons except you know, |
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| 50:20 | not sitting under a set of you're just looking at the computer screen |
|
| 50:24 | a mouse you know. But the is the same is a reconstructed cells |
|
| 50:30 | Harmonica Hall did but he did it Golgi stain. This is a different |
|
| 50:35 | , this one and this one we exactly what cells pick it up. |
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| 50:38 | the south in which we inject or biocyte in. Yeah, good |
|
| 50:48 | Alright, phosphor lipid bi layer. why are we going to talk about |
|
| 50:53 | ? We're gonna talk about it because gonna talk about a little bit about |
|
| 50:58 | structure of neurons and how they have excited inhibitor synopsis. And then we're |
|
| 51:06 | wait and then we're gonna move into communication of neurons. But so let's |
|
| 51:13 | a little bit of some basic stuff as a reminder for some of you |
|
| 51:18 | are surrounded by plasma membrane. It's phosphor lipid bi layer possible, lipid |
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| 51:23 | layer is composed of fossil lipids and have their hydro filic heads. So |
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| 51:32 | is the head which likes water. polar charged and is attracted to this |
|
| 51:38 | environment on both sides of extra cellular and the inter cellular environment. And |
|
| 51:45 | it has a hydrophobic tails. And are fatty acid tails that come inside |
|
| 51:54 | form the inside part of the phosphor by later in the phosphor lipid |
|
| 51:59 | you have cholesterol that's embedded and cholesterol for tighter interactions of the foss Philip |
|
| 52:08 | and a lot of times influences the of like the structural plasticity of the |
|
| 52:16 | lipid bi layer. Then you have literally illustrated here that are very important |
|
| 52:24 | self cell recognition. You have carbohydrates sugars. So cells all cells and |
|
| 52:32 | are like sugar coated with carbohydrates and you have proteins that are recognition |
|
| 52:40 | You have receptor proteins and you have proteins. And so when we talk |
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| 52:47 | neurons, what's, what's really important understand is that this phosphor lipid bi |
|
| 52:54 | is fluid, this and the the the proteins, the channels can move |
|
| 53:04 | possible lipid bi layer that this forceful bi layer will allow for the lateral |
|
| 53:11 | of these structures, basically of protein structures through the phosphor lipid to travel |
|
| 53:18 | the south underneath the phosphor lipid bi is supported by the side of skeletal |
|
| 53:25 | . And these side of skeletal elements arrange rearrange. Ellen gate shorten themselves |
|
| 53:34 | themselves in higher densities stack themselves in densities. These side of skeletal elements |
|
| 53:40 | the overall shape and hold up the shape of the plasma membrane. And |
|
| 53:46 | if you rearrange the side of skeletal make them really sparse. For |
|
| 53:52 | the membrane may dip. It may have enough support and may start rearranging |
|
| 53:57 | the fossil lipids may exit out and themselves in in in in the slightly |
|
| 54:04 | um situations here in the membrane there's dependent process, meaning that as the |
|
| 54:14 | get activated as these receptor channel proteins activated by chemicals. This fluidity and |
|
| 54:21 | movement of molecules and the movement of across membranes will also be influenced. |
|
| 54:28 | you have shaping of the movement and of what structures are found by by |
|
| 54:37 | . Yeah. Side of skeletal We have micro tubules, neuro filaments |
|
| 54:43 | micro filaments. So micro tubules are largest elements and micro filaments are the |
|
| 54:50 | elements acting molecules make the micro filaments active molecules can prelim arise together and |
|
| 54:58 | into longer chains. Or they can broken up or they can depolymerization to |
|
| 55:03 | chains and active molecules will be located the outermost address of the plasma |
|
| 55:10 | So they are the most small and most mobile side of skeletal elements. |
|
| 55:15 | there is more support needed, they'll up their chains and their lattices to |
|
| 55:21 | the membrane and likewise, they can depolymerization to shorter chains. Lesser densities |
|
| 55:28 | these lattices. Um provide less support the plasma membranes. Micro tubules is |
|
| 55:35 | here is a cross section through the and as you can see this is |
|
| 55:42 | that surrounds the axon. This is layer so it's like sheets of |
|
| 55:47 | This will be the likud emphasize We talked about the wheel cells that |
|
| 55:52 | wrap around the axons. So you'll layer upon layer layer upon layer of |
|
| 55:58 | installation of myelin. This is the inside of the axon amazon myelin. |
|
| 56:06 | inside the axon you see these lines and they almost look like these very |
|
| 56:13 | blood vessels. But they're not blood . They are micro tubules and micro |
|
| 56:22 | are very important for cellular transport. there are larger elements. The larger |
|
| 56:29 | elements, the closer to the core the soma and nucleus are going to |
|
| 56:34 | found. The smaller the elements like filaments are acting as the the further |
|
| 56:41 | they will be in the distal regions support the outer edges of the plasma |
|
| 56:47 | . The micro tubules will be responsible transport. Ectoplasmic transport, cellular transport |
|
| 56:55 | general, but mostly concentrated around the . Where actually a lot of things |
|
| 57:01 | by synthesized, produced and need to transported out of the selma or brought |
|
| 57:06 | into the selma. So, you decided skeletal elements. And before we |
|
| 57:18 | into I want to see when I to talk about the ion channels. |
|
| 57:21 | think I'm actually gonna wrote it on board. But I'm going to talk |
|
| 57:25 | ion channels maybe in the next But let's talk about something that is |
|
| 57:31 | to neurons. So this is not to neurons. You know, axl |
|
| 57:36 | transport micro tube side of skeletal This is not unique what is unique |
|
| 57:41 | neurons as axons. Action potentials. then you say okay but then there's |
|
| 57:47 | there's muscle action potentials. Yes there . But eurostar, the fastest action |
|
| 57:53 | . Okay, so what else is to neurons? Dendrites and dendritic |
|
| 57:58 | These processes information of the synopsis, number of the synopses that are being |
|
| 58:05 | . The amount of time, the by which neurons can integrate and process |
|
| 58:09 | of that information. That is that what is unique. Some neurons |
|
| 58:15 | when we talked about those frequencies of potentials. Karam it'll cells will typically |
|
| 58:21 | the excited or parameter cells will typically three to 10 births, their action |
|
| 58:33 | and inhibitor inter neurons can fire up 600 action potentials a 2nd, 600 |
|
| 58:49 | . So some of these cells are fast. They can produce very fast |
|
| 58:55 | of action potentials and others are But you can't imagine that there's nothing |
|
| 59:03 | I can think of that is that that is faster apart from maybe I |
|
| 59:11 | know, vibration, McCann oh, processing in the air and the |
|
| 59:21 | Um But no other cells that are sensor in the tissue that I can |
|
| 59:30 | of that can operate at speeds like . And so inter neurons are not |
|
| 59:37 | a variety of cells, it's also variety of firing patterns, variety of |
|
| 59:42 | . Which is very important because inter can be slow, can be stuttering |
|
| 59:47 | be bursting can be super fast. a variety which will contribute to the |
|
| 59:54 | of processing that we can do. so now what's very important is with |
|
| 60:02 | discovery of the election microscopes we were to visualize the synapse is. Most |
|
| 60:07 | the synopsis on neurons are formed on dendritic spines. So dendrites will have |
|
| 60:14 | protrusions that are only about the Dendritic shaft is about one micrometer in |
|
| 60:20 | . So these protrusions can be one meter to two micrometers in length and |
|
| 60:25 | thinner than one micrometer in diameter. referred to as the spine. So |
|
| 60:31 | is an electron microscope image which shows pre synaptic terminal in red. And |
|
| 60:36 | round organelles are vesicles that are going be filled or are filled with |
|
| 60:44 | If the axon is excited, external and deep polarization external terminal will cause |
|
| 60:50 | fusion of these vesicles. The release the neurotransmitter into the synaptic cleft is |
|
| 60:56 | space of about 20 nanometers that separate neuron from another. And then these |
|
| 61:02 | will buy into the post synaptic receptors are located in post synaptic density. |
|
| 61:06 | D. N. Stands for dendrite stands for post synaptic density. And |
|
| 61:12 | you can see there are mitochondria in dendritic spines. There's also in the |
|
| 61:19 | spines complexes and that's important because they energy. Dendritic spines, mitochondria because |
|
| 61:31 | have Paula ribosome complexes, they're capable post translational modifications right there at the |
|
| 61:39 | of the dendritic spine without going back the summer and saying, hey I |
|
| 61:45 | this and that to a certain So there's somewhat biochemical independent from the |
|
| 61:52 | but they can influence and somewhat are of course because they're part of the |
|
| 61:58 | so they're not like unattached, They in different shapes. Typically they described |
|
| 62:05 | studies of their shorter ones, this in green, this is a study |
|
| 62:12 | spine. You can have a thin which is this is a thin spine |
|
| 62:17 | purple. Then you have a mushroom it looks like a mushroom cap. |
|
| 62:24 | end of that spine shown here in . So they come in different |
|
| 62:30 | They come in slightly different sizes. I think predominantly three maybe five different |
|
| 62:38 | that you can distinguish. These They are the most plastic units and |
|
| 62:46 | most malleable units in neurons and neuronal . You can strengthen dendritic spines, |
|
| 62:56 | can weaken the spines, you can new dendritic spines and you can eliminate |
|
| 63:02 | existing dendritic spines, you can change numbers and you can change their |
|
| 63:08 | This is again activity dependent and environment process and activity dependent plasticity plasticity in |
|
| 63:16 | sense that you can strengthen or you build a new synopsis. So when |
|
| 63:20 | learning new information, we are typically have finite amount of information that we |
|
| 63:26 | keep and there's certain type of information is really important for us now the |
|
| 63:34 | this year, maybe, maybe this . And it's not gonna be the |
|
| 63:40 | information that's important next decade or the year even. So, as you |
|
| 63:47 | acquiring new information and learning, you doing all of these things. You |
|
| 63:53 | building new synopsis, synopsis and new spines. You're forgetting certain things and |
|
| 64:00 | making room for new things. So going to eliminate some gendered experience or |
|
| 64:09 | going to weaken them, you're gonna keep them right. But if you |
|
| 64:14 | review that material for the next two , it will be very vaguely. |
|
| 64:18 | very weeks and I think spine will be there. And then if you |
|
| 64:25 | the material two years later, maybe will strengthen again and you'll come back |
|
| 64:29 | that knowledge. So all of these , its activity dependent processes. So |
|
| 64:35 | you're focusing on is the activity. focusing on certain material with a certain |
|
| 64:42 | of activity, a certain task at type of activity. Certain sensory |
|
| 64:47 | you like, art versus music, two different sensory types of input that |
|
| 64:52 | uh practicing with or you know, stimulated with constantly in your brain. |
|
| 65:00 | something like both. Now, dendritic are also distributed along dendrites in a |
|
| 65:12 | manner. It's not that we understand and can predict, oh, if |
|
| 65:18 | look at the cell, this is subtype of cell because it has this |
|
| 65:21 | of the grid expands. But what do know is that abnormal formation of |
|
| 65:27 | spines such as in fragile X So and introduce this. We're gonna |
|
| 65:50 | back and talk about this a little more next lecture because I'm running out |
|
| 65:53 | time. But if you don't have proper shapes of these funds, if |
|
| 66:00 | don't have the proper distribution of these of contact along the dendrite, it |
|
| 66:05 | lead to mental retardation and the conditions as fragile X syndrome. And it |
|
| 66:12 | a mental formal recommendation that has certain common with autism and also typically a |
|
| 66:22 | morbidity as apple, etc. And . So it's pretty severe condition and |
|
| 66:32 | severe retardation. And what we're seeing these cases will actually describe a little |
|
| 66:38 | of the background to this next lecture it's dependent on the expression of a |
|
| 66:45 | protein called FM RP. Uh And the done right, you can see |
|
| 66:54 | dendritic shaft here on the left here from a normal and fund on the |
|
| 67:01 | . It's from mentally retarded in And you can very clearly see that |
|
| 67:08 | a difference in morphology of these dendritic density distribution. Therefore they're very important |
|
| 67:17 | normal information processing and encoding normal formation distribution of these spines and their shapes |
|
| 67:23 | everything. Points of contact is very for normal development of the brain. |
|
| 67:30 | as you can see in this image I'm going to discuss is the last |
|
| 67:34 | today is what you're seeing is you that each neuron okay, can receive |
|
| 67:42 | in green or glutamate ergic synopsis. everyone of this punk Tate is the |
|
| 67:50 | , dermatologic synapse That is stained for glutamate receptor. Each one of these |
|
| 67:58 | punkt, eight Gaba receptors, I hear that there is synopsis. So |
|
| 68:05 | this again speaks to the complexity of that this neuron has to take from |
|
| 68:16 | thousands, tens of thousands, excitatory with inhibitors and absence. And it |
|
| 68:25 | to happen in a really specific pattern connectivity to those synapses to those dendritic |
|
| 68:35 | that are located in specific areas of downright that will communicate that information in |
|
| 68:40 | correct manner for neurons to process. and by the way, we all |
|
| 68:48 | slightly different connectivity in our brands. all underwent different genetic and environmental |
|
| 69:00 | so to speak as we were growing and we are pruning some of these |
|
| 69:09 | were actually born with a lot more the synopsis and the good experience that |
|
| 69:16 | find ourselves into adulthood. So during early process of development and plasticity, |
|
| 69:23 | lot of what is happening is that is connected to everything And as you |
|
| 69:30 | things as your infant and you're learning colors things like that. This connectivity |
|
| 69:38 | start disconnecting from each other and things are exercise that you're exposed to censor |
|
| 69:44 | they strengthen and the other one's weaken go away. But in general you |
|
| 69:50 | lesser number of synapses and lesser number dendritic spines as adult, as opposed |
|
| 69:59 | as a newborn infant or very early brain. Even so that's why it's |
|
| 70:09 | important for overall computation of this neuron the brain have dendritic spines have certain |
|
| 70:15 | of the spines, densities and sub distribution localization of those parts. |
|
| 70:21 | we'll end here today, and when come back, we'll pick up where |
|
| 70:24 | left off. I'm gonna spend a bit of time talking about what fragile |
|
| 70:28 | and FM RP. So we understand uh predict spine and abnormalities in a |
|
| 70:34 | better way. Thank |
|
