Types of neurotransmitter receptors: Musacrinic ACh receptors: these are generally inhibitory. When ACh binds with a G protein receptors that activates a K channel, that allows the K to leave the neuron, and then hyperpolarize the neuron. So that?s a positively charged ion leaving the neuron. As far as G protein coupled receptors that create adenylate cylcases, and phosphotases. Let?s talk about those next. In the case of creating cyclic AMP, neurotransmitter binds with its receptors, activates the G protein. The G protein is coupled to an effector system. One of the G unit subunit (alpha, beta, or gamma) binds with and activates the adenylyl cyclase, which creates cAMP. And then cAMP acts as a second messenger. cAMP can do a couple of things and it depends on the receptor types: It can bind directly with an ion channel and open or close an ion channel. So depending on the nature of the ion channel, if it would?ve opened a Na channel, and allow Na influx, then it would depolarize the neuron, and reduce the amount of depolarizing current necessary to reach threshold. But generally opening of these types of ion channel, doesn?t provide enough current to actually reach threshold. It simply changes the resting state, either increasing or decreasing the amount of depolarization necessary to reach threshold. Another thing cAMP could do is activate a protein kinase. Typically we are talking about PKA (protein kinase A). That kinase then phosphorylates some target structure often an ion channel regulating the way the ion channel works. For example: when glutamate binds its receptors it opens a Na channel. At the same time, that neuron has been modulated by a modulatory neurotransmitter that produces cAMP that then activates protein kinase A which then phosphorylates the ion channel making it less efficient in Na conductance and then we end up with a circumstance where it?s more difficult to reach threshold. 2nd messenger that includes phospholipase C: Neurotransmitter bound G protein is activated, G protein coupled to an affector protein that produces phospholipase C. That then produces 2 other 2nd messengers: DAG (Diachyglygerol) and IP3 (Inositol triphosphate). IP3 can cause intracellular Ca to be released from the endoplasmic reticulum and then Ca can mediate a number of different intracellular effects including altering Ca production to ion channels, etc. DAG phosphorylates/ activates PKC which then regulates a number of different ion channels. Last mechanism of 2nd messenger function is the CREB system: CREB system is involved in upregulating or downregulating expression of specific gene sequence. Neuro anatomy Nervous system in embryological state: When the nervous system is forming. We already got the blastula, ectoderm, endoderm, and mesoderm, we already got through gastrulation, we got 3 germ layers. On the surface, the ectoderm begins to migrate inwardly. If we look at this process cross sectionally, we?ll see the ectoderm migrating in, what ultimately happens is, it creates a tube along the dorsal surface. This tube surrounds a fluid filled cavity called the ventricle. Depending on the evolutionary hierarchy, the nervous system might just be this tube. In our development, the anterior end forms a head, the fluid filled will eventually become the ventricular system. The nervous system develops a head end (anterior) and a tail end (posterior). Typically most structures, even in the brain, are bilaterally organized, along some longitudinal axis that runs from anterior to posterior. Things that lie closer to this axis is medial and things that lie further from the axis is lateral. If we look at it from the side, it has a upper surface (dorsal) and a lower surface (ventral). In many advance nervous system, as the nervous system forms, the anterior end, it not only forms the tri parted brain, that brain eventually folds in on itself, with the most anterior structures fold in. as a consequence, the brain ends up having 2 long axis. One that is running through the spinal cord, and one that is running through the long axis of the cerebral hemisphere. So a single structure can be both dorsal and ventral: like the cerebellum is ventral to the longitudinal axis of the forebrain, and dorsal to the longitudinal axis of the brainstem and spinal cord. We also use rostral instead of anterior for the brain, and caudal for posterior. At some point during the evolution of our nervous system, when eventually the physical size of the cranial ball became fixed, and we still wanted to acquire additional capacity to our nervous system. The number of neurons is proportionate to the capacity of the nervous system. So to increase number without increasing the physical mass of the brain, modifying the brain in a different way. So we simply had our brain folded like an accordion. So many advanced organism like primates and dolphins, their brain surface is highly convoluted. The folds are called gyrus and the sulci that lie in between. If we take the brain and section it. The surface folded. All those neurons are in a thin sheet only near the very very surface of the brain. The neurons near the surface of the brain are organized in layers called the cortex. 95% of the mass are axons that run between different regions of the brain. The connection that are formed in the cortex has to go through a circumscribed pathway to reach other parts of the brain. Because the cell bodies and dendrites are not myelinated, so the color of the cell bodes and dentrites are grey. So the generic term grey matter refers to the cell bodies. So the surface is predominantly grey matter and the central areas are white matter. The upper part of our brain, especially the hemispheres are organized in layers called cortex, and so we do have populations of neurons that are sub cortical, deep inside of the brain itself. Much of the advanced neocortical brain are tributable to neurons being laid out on the surface of the brain. Cortex is a property of more advanced evolutionary development. In the brain itself, the central regions are predominantly white matter. Since brain is a 3D structures and most of the structures are not on the surface of the brain, other than the cortex. We have to be able to systematically section the brain in order to study the organizations. 3D structures that separates the top and the bottom is a horizontal plane. A plane that separates left and right, is sagittal. Coronal is a cross section for the brain. The brain is bilateral and if we have structures ABC on one side and DEF on another side, and we refer to A and B which are on the same side, they are epsolateral. If we refer to D and A which are on different sides, they are controlateral. Sometimes we need to describe position of something to some fixed points, so if we compare thochlea and carpals with referece to the scapula, the throchlea is proximal and carpals are distal. So distal and proximal has no fixed value, just depends on what you are comparing it to. Terms referring to neuron cell bodies and axons: Most neurons are organized as cortex. Anything that is a cell body is generically called grey matter, whether its cortex or subcortex. Subcortical structures that aren?t organized in layers fall into 4 categories: nuclei, locus, substantia, and ganglion. Nuclei are very large, well defined populations of cell bodies. Locus are very small, well localized populations of cell bodies. Substantia are very large populations of cell bodies, but not well defined. Ganglions are collections of cell bodies that are in the peripheral nervous system. We don?t have any ganglions in the brain or spinal cord. As far as white matter is concerned (the term is derived from the yellowish appearance of the myelin): Fibers: a term that describes a single axon that?s myelinated. Tracts: are a collection of fibers that share a common originating structure and target structure. Commisure: a bundle that crosses from one side of the brain to the other. The biggest commisure in the brain is corpus callosum (a huge fiber tracts that runs between the two hemispheres). Bundles: collection of axons that run together but doesn?t share any originating structure or target structure. Nerves: there are no nerves in the brain. There are no nerves in the spinal cord. A nerve is a collection of axons in the periphery. Some collection of axons that are connecting the spinal cord to the target tissue, like a muscle, or some collection of axons that are coming back from some sensory receptor in the periphery going to the brain, like optic nerve. The nervous system is divided into 2 different components. The central nervous system and the peripheral nervous system. Central nervous system includes the brain and the spinal cord. These are normally surrounded by bones. Peripheral nervous system includes an autonomic division and a somatic division. The brain: You can divide the brain into 3 functional regions (they don?t come from common embryological source): Cerebellum: Cerebrum (cerebral hemispheres): the 2 hemispheres are characterized by having many folds and sulcus. Some common physical characteristics of the brain are: a sulcus that separates the anterior part of the brain from the posterior, central sulcus. Then there?s a major sulcus that separates the more ventral aspect of the brain from the more dorsal aspect of the brain, sometimes known as lateral sulcus or Sylvian fissure. (Fissure is a very deep groove.) if we look at the brain from top down, the groove that separates right and left is called the superior longitudinal sulcus. There?s a sulcus near the back of the brain, that separates the occipital from the parietal lobe, parieto-occipital sulcus. Given those landmarks, you can divide the brain into 4 regions. The most anterior lobe is the frontal lobe. The lobe that lies immediately posterior to the central sulcus is the parietal lobe. The lobe that lies posterior to the parieto-occipital sulcus is the occipital lobe. The lobe that lies inferior to the sylvian fissure is the temporal lobe. Each one of those lobes have a number of gyrus and within those gyrus are functional organizations of neurons that give rise to higher cognitive functions. If we wanted to assign some limited functionality to any given lobe, we would say the frontal lobe is predominantly movement and higher cognitive functioning, the parietal lobe is the primary regions for somatic sensory processing and spatial thought. The temporal lobe is primary auditory functioning and language recognition and formation plus a lot of processes like consolidation of memory. The occipital lobe is almost exclusively visual. The function of each one of these gyrus has been mapped and determined. The system of naming them is called the Brodmann system. For example, the gyrus that?s immediately anterior to the central sulcus is the precentral gyrus, which is primary motor functions. So when we execute actual contraction of a muscle, the signal comes from the precentral gyrus, probably Brodmann area 4. The gyrus that?s immediately posterior to the central sulcus is the post central gyrus, primary somatic cortex. Looking at cortex: If we take a section of the brain, we?ll notice the surface of the brain is primarily where the neurons are concentrated. If we then take a small surface area anatomy and look at it at a cellular level, that cortext, is series of layers. There are 6 layers in cortex. Hippocampus is 3 layers. Most cortex is 6. They layers are given roman numerals. Within these layers, the neurons are organized and functionally connected. In each given regions of the cortex some specific functionality is associated with that region. In human and other advanced nervous systems, the information about all other cortical and noncortical areas must be shared among every part of the brain. So if we want to perform some complex task, like chalk being thrown back at the professor, there?s no single area that could do that. In every given region of the brain, we have these microcircuits that serve one specific functionality. Then at the same time, coming into this microcircuit is information from every other functionality. How the cortex is designed: first we need a layer where all the connections are formed, and that?s the top layer, layer I, which is called the molecular layer. In the molecular layer, that?s where the dendrites of the cells exist. So the cells dendrites are going to be in layer I and its axons are going to be somewhere else. So each of these layers have cells in them which sends their dendrites in the molecular layer. In layer II and III, they are populated with particular kinds of neurons called pyramidal cells and so are layer V and VI. Layer IV has cells that looks like little stars and they are called stellate cells. During watching a movie, we have other cortical information coming into II and III and that information then synapses up in the molecular layer, affecting the cells that projects out. Layer IV is the primary input from the thalamus. Thalamus is where all the primary sensory information goes first. Primary information about visual or auditory goes to layer IV from thalamus. Layer V and VI is primary subcortical and spinal cortical projections. The information will come in and then processed and then send back to where it came from, now with new integrated information about other cortical activities, other sensory activities. Not all of the brain is cortical. some parts of the brain are subcortical, collections of neurons that are not organized in layers. When neurons lie in a series, that?s perpendicular to the surface, it?s called a column. When neurons lie parallel to the surface it?s called a row. There?s a number of subcortical structures. The most important grouping of subcortical structure is called diencephalon. Diencephalon is a grouping of 3 different structures: the thalamus, hypothalamus, and the epithalamus. If we cut the brain mid sagitally and thalamus would be right in the centre of the brain. They hypothalamus would lie immediately below the thalamus, hence hypothalamus. Then we have a number of other structures that are epithalamus: pineal gland, coroid plexus. The thalamus, is kind of a relay, takes incoming information from primary sensory structures, from motor structures and relays it onto the appropriate cortical area. Thalamus is not limited to that. There are many neurons in the thalamus that are involved in other functions. They hypothalamus has 3 functionality: autonomic, behavioral, and neuroendocrine functions. Hunger, thirst, regulation of circadian rhythm, all hypothalamic. Although we evolved away from some behavioral, but still feeding behavior is hypothalamic. But in lower animals, lots of preditorial and territorial behavior are all hypothalamus. The last part of the diencephalon is the epithalamus. It?s 2 different things: pineal gland and coroid plexus. Pineal gland is secretory tissue from an epithelial cell lines migrated during embryological development into the brain cavity. Pienal gland produces a secretion called melatonin which doesn?t make you sleep but affect the circadian rhythm. Choroid plexus is also secretory tissue but ends up in the fluid filled chamber called the ventricles. Choroid plexus produces CSF (cerebral spinal fluid). These groups of 3structures are grouped together in diencephalon, but they are not functionally interconnected. Whereas if we take the limbic system, the basal ganglia or the reticular activating system, these are collection of structures, often distributed, broadly throughout the brain but are functionally interconnected within circuits to give rise to higher functionality. Limbic system involves multiple brain structures, all functionally interconnected to give rise to what we call emotion. Basal ganglia includes many structures all working collectively to modulate movement. Reticular activating system, multiple brain stem structures, controls ascending and descending information into the cortex. These systems are all subcortical, but they way they are interconnected give rise to higher functionality. Brain stem:
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