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Ted Petit

Lec 1 Basic structure of the nervous system. • the nervous system - central (central nervous system) and peripheral (peripheral nervous system) • central - brain and spinal cord. • peripheral - everything other than brain and spinal cord - the nerves in our body. • the brain is a continuation of the spinal cord - during evolution it looks like a tube - like a straw • brain and spinal cord - evolution and development - one end develops more than the other • gets more bumps - starts to look like another structure. Basic components of the brain. • brain - starting from the most posterior part of the brain - closest to the spinal cord..... HINDBRAIN 2 major components: medulla • basic life processes. • keeps heart beating, respiratory system going, etc. cerebellum • cabbage at the base of the brain. • sensory and motor integration. • damage - can't walk upright etc • alcoholics - damages cerebellum. MIDBRAIN • there are different components to it. • reticular formation is in the midbrain. • the reticular formation - involved in sleep-wakefulness. • damage here might put you in a coma - no sleep wakefulness. • gunshot - makes reticular formation fire - you wake up really fast. FOREBRAIN • thalamus - relay station - relaying information to the cerebral cortex - all information stops here for a while - relaying information from here - like Bell Canada. • hypothalamus - smaller, under thalamus - basic body functions - flight or fear - fighting - feeding - the 4 Fs - flight, feeding, fighting, and sexual reproduction - also remember it as - if it feels good - than it is probably in the hypothalamus. In the forebrain. The limbic system • emotion and emotionality. • amygdala - involved in emotion, aggression, happiness, sadness • hippocampus - • some people put hypothalamus here too - i.e. it has emotional aspect as well. Notice that these don't keep you alive - but give you emotional repertoire - this is a network of structures which are tied together. Olfactory - in animals very important for everything - but in humans - we don't depend on smell so much but limbic system still plays the role in everything to do with emotion and aggression and some sexual stuff. At the front - we see the cerebral cortex - or neocortex. This is all forebrain • this neocortex - deals with higher brain functions. • intelligence • speech • this curls back and covers the rest of the brain&ldots; so in humans - cortex is huge. • dolphins seem more evolved than us - more convolutions, more weight to total body weight. Evolution of the nervous system • brain in human is increased in size. • even rat brain is much bigger than turtle. • gets more bumps so it can do extra stuff. • one end started to develop more in higher guys. • the forebrain has started (even in fish) - to get larger relative to other parts of the brain. • since skull will not grow - the cortex gets pushed back and covers everything else. • only thing left is cerebellum. • also, behavioural repertoire of animal is correlated with brain parts. • i.e. there is a direct correlation between what the animal can do and what his brain parts look like. • if an animal depends on vision - that part of the brain - will be bigger • animals that deal with balance - i.e. birds - have larger areas of the brain that deal with that. • olfactory bulb - in rat - is quite large - because they deal with smell • our olfactory bulb is quite small. • so through evolution - forebrain gets larger - and those things that the organism does best - gets the largest in their brain. • size of cortex is related to intelligent behaviour. Development of the brain • phylogeny recapitulates ontogony. your phylogenetic development - your development as a species Ontogony - your development as an individual. If you look at the way we development from conception to adulthood - it goes through the same steps that we did as a species. We get gill slits, mamillary organs, a tail - we get those as we start to develop - this is also seen in development of nervous system. Like the primitive organisms - initially the nervous system looks like a tube - at 7 weeks - it is more complicated but still very simple. At 9 weeks - the forebrain in humans gets bigger and pushes everybody else away - it pushes until its full - then it starts to convolute - this is done during phylogenetic and ontogenetic. This cortex in human looks like its most of the brain - but remember this is the anterior structure of the brain - it starts at the front - so if cortex is damaged - we have hit the most anterior and thus most evolved structure of the brain - this is bad. As organisms have developed - they have added on more parts - the most recent is always anterior. So the most forward and thus most new in our brain - is the cortex - hence neocortex. Triune brain theory. MacLeans • 3 parts to brain functioning. • oldest portion of the brain - the reptilian brain - or the hind brain - or brain stem - i.e. the basic core of the hind brain. • found in reptiles. • there to form basic life processes. Next we added.. paleo mammalian brain • here he was referring to the limbic system (emotions) i.e. we still have reptilian brain - we just added other things to it. Finally we add.. neo-mammalian brain. • this is the cerebral cortex • this lets us add the repertoire of intellectual behaviour. • read, write, language, study. • always remember - we don't lose those old brains - we just add some on. Within every human there are 3 brains - paleo-mammalian, reptilian, neo-mammalian. As the brain has evolved - primitive in brain stem - then more anterior - is more complex - so the further up it goes up - the more complex but the less life threatening it becomes. Always keep this in mind. Stroke in cortex - call therapist Lec 2 Cerebral cortex • divisions • functions • anatomy • blood supply. • it has convolutions - not flat - it had mountains and valleys. • valleys - sulci - sulcus is singular • mountains - gyri - gyrus is singular. • top view - divided into left and right hemisphere. • each side controls the contralateral side and gets its information from the contralateral side. • paralysis on the right side - damage to the left side. • some of indentations are quite large - large ones are fissures. • fissures divides the brain (cerebral cortex) into different lobes. • central sulcus (or fissure) - sylvian or lateral fissure - up the side of the brain. • longitudinal fissure - brain into right and left hemisphere. • the two hemisphere are connected - corpus callosum - large fibre band. • these large fissures divide the brain into different lobes - fronta is the most anterior. Parietal lobe behind central sulcus. Occipital - posterior portion of the brain. Temporal lobe - base of brain - separated from sylvian fissure. • divide the lobes not only because of their anatomy - but because each lobe has it's own particular behavioural function. • frontal - motor behaviours. • parietal - sensations from the body. I.e. somatosensory. Soma means body. I.e. it is not vision - vision is not somatosensory. • occipital - vision • temporal - auditory information. Important function in speech. • each lobe has it's primary function which is a basic function - then it does higher order things • each lobe has a primary area. Or we can say it has an area of primary cortex. Then there is associational cortex or secondary areas. • primary areas do principle actions. • Brodmann's areas - each lobe is broken up into certain areas. He put numbers on the cortex. • frontal lobe - motor output - the primary motor area or strip - information goes out of the cortex here - so guy can't move if problem here. • the rest is associational - they do much more complex things - they plan the motor movements - they think about them in the future. • occipital - area 17 is for vision - putting shapes together and stuff is associational. • as we go through evolution - the more evolved - the more associational cortex there is. I.e. we have more higher order complex things. • in human - most is associational. Frontal lobe • motor control • motor movements. • moves until central sulcus. • this is the function of it's primary strip (the motor strip) • it's associational cortex is for planning of motor movement. • pre-central gyrus - easy to remember - we have a central sulcus - the little mountain in front of it is a pre (in front) central gyrus - this is the primary motor strip in the brain - just anterior to the central sulcus. • the precentral gyrus is organized in a very specific manner. Brodmann's areas 4 and 6 are the primary motor strip. I.e. it controls toes one by one in order then torso then fingers one by one - so if you get a tumor - you know where his brain was hurt - you know it's opposite side - if his foot can't move - I know it is frontal lobe at the top. • homunculus - little person - but a distorted view - it seems like the representation in the brain isn't correlated with anatomy but with what we have more control over. I.e. if we need lots of control over our mouth - it is bigger. • our fingers need a lot of control and so does our mouth and lips - so they are well represented there (in the primary motor strip) parietal lobe • starts at central sulcus. goes back to occipital lobe. • body sensations. • has a primary area and associational area. • it has a somatosensory strip in the post central gyrus. • i.e. just behind the central gyrus. • the strip has Brodmann's areas 1,2,3. We are automatically talking about the primary somatosensory strip - i.e. the post central gyrus in the parietal lobe • it is also very linear and has a little homunculus. • both the sensory and motor • genitalia are on sensory side. • most sensitive parts of body have more neurons - so are represented larger. • lips and hands and genitalia are big on this sensory strip. Occipital lobe • vision • Brodmann's area 17 - the primary visual receptive area. • all stuff from eyes goes to that area. Temporal lobe • ventral to the sylvian fissure (or lateral) • hearing • has primary auditory receptive area -Brodmann's area 41. • no homunculi here - just the eye - so it doesn't need a little person. Cerebral ventricles • spinal canal - filled with cerebro spinal fluid - it is continuous with the spinal canal. • first two are known as the lateral ventricles. • they are lateral because there is one on each side. • cerebo spinal fluid has a different density than neurons. • a tumor will stress the ventricle and distort it. • in AD - brain shrinks - and ventricles enlarge to fill the space. • 1 and 2 are on the sides - they are all connected • third ventricle - inside the thalamus - in the diencephalon (the mid brain) • continues via cerebral aqueduct into fourth ventricle (found in hind brain near the cerebellum). • continuous flowing and eventually is absorbed. Vascular supply • two primary sources to the brain - vertebral arteries and internal carotid arteries. Easy to remember - comes up the vertebrae. • basilar artery - easy to remember - they join here at the base of the brain. • circle at the base of the brain - circle of Willis. • internal carotid arteries attach the circle of Willis. • circle of Willis - all are connected because of this - if you lose some entrance - you still get complete circulation in the brain. It is a backup unit and very important for life. • there are 3 cerebral arteries - anterior cerebral artery, middle cerebral artery, posterior cerebral artery. • anterior - supplies anterior, medial, and dorsal portions of the brain • middle cerebral artery - goes up the sylvian fissure - and supplies the lateral surface (side of the brain.) • posterior cerebral artery - supplies posterior portion of brain and ventral area and posterior medial. • when a piece of cholesterol breaks off and clots your blood - this affects the way you function • if it hits anterior cerebral artery - it might hurt - toes paralysis etc. • if clog is in middle cerebral artery - this hurts temporal lobe - and you lose hearing. • tissue far from heart - dies - i.e. perimeter of brain dies if you sit in your car in your garage for a long time - so the speech centre is isolated from brain - speech is in tact but sitting there all by itself. • they can speak but it doesn't connect with any knowledge that the person has - this happens with any kind of anoxia. Coverings of the brain three coverings... meninges. • first covering from outside is the dura mater - thick tough membrane. • next covering - arachnoid - spongy - below the arachnoid - is the sub arachnoid space - this is where the blood vessels course through - they are below the duramater and below the arachnoid and found in the subarachnoid space. • Pia mater - thin, delicate - sticks to the cortex - it follows the convolutions. • elderly people - have hemorrhaging - hematoma - most are subdural - just below the dura - pressure just below the brain - relieve the pressure - person will heal fine - it is easy to do - so you are lucky if it a subdural hematoma. Lec 3 Today. Globally - what can go wrong with the brain? Pathologies neurons Vascular Disorders something goes wrong with blood supply. these lead to cerebral vascular accidents - or most times strokes. loss of blood supply, and thus loss of oxygen and food to the brain. when blood flow is lost from the brain - this produces ischemia. most important is that we lose oxygen - fatal very quickly - we automatically think about loss of oxygen although other things are related as well. ischemia produces dead or dying tissue - known as an infarct. recapping: vascular accident or stroke leads to ischemia which leads to an infarct. these can be slow or rapid slow - leads to slow death of tissue - i.e. the tissue gets softened and starts to die - encephalomalacia. From loss of blood supply. fast - leads to a stroke. these accidents are caused by 3 typesŠ. thrombosis - blood clot formed locally - not all strokes are from this local thrombosis embolism - other's are caused by pieces falling off from one of the arteries in another part of the body and getting caught in the brain in a blood vessel - this is an embolism - so both of these are causes of blood supply - next causeŠ slow general reduction in blood supply caused by generalized reduction in blood flow through the arteries - e.g. arteriosclerosis. This isn't sudden - it also isn't a clot - it is a slow loss of blood supply. This is more permanent then the next example of TIA. understand the distinctionsŠ.. TIA - transient (short term) ischemic attack. vasculature closes down from muscular contraction. it isn't enough to kill the tissue - but makes it dysfunctional when it relaxes - everything is restored - hence it is transient. common in migraines. loss of vision - sometimes happens. Those were cerebral vascular problems - next are some things that are different than embolisms and thrombosisŠ. Cerebral Hemorrhages. massive bleeding into brain matter. caused by high blood pressure. these are fun also. not enough elasticity in there - bursts - hurts that area of the brain. Angiomas abnormal collection of blood vessels. congenital - you are born with them. they are weak by their nature. they have a tendency to rupture. arterial blood may go directly to venous area - this is bad - doesn't get to give it's rich oxygen and nutrients. Aneurysms analogy - car on 401 - one of his tires has a balloon part out - it's about ready to burst blood vessels start to swell and enlarge - clowns with long skinny balloons - you get the bulge - same phenomenon - the elasticity breaks down and you get swelling there - it might burst localized deficit in elasticity. When it bursts (an aneurysm) or hemorrhaging - causes sub-dural hematoma - it is not a cerebral hemorrhage - it is outside brain - between brain and skull. it pushes the brain aside - not good - so do some power drilling - it will drain out - cool at parties. ventricles - not at centre anymore - all ventricular fluid has moved to the other side also - pressure has squeezed the CSF out of one and into the other - typical of sub-dural hematomas. An aneurysm is not a stroke - it can lead to one - a hemorrhage could be called a stroke if it were really small - we don't have to call it that though - a stroke is any sudden bad blood thing involving the brain. Stroke - loss of blood usually. Hemorrhage - problems with more blood Closed Head Injuries automobile accidents, motorcycle. blow to the head predictable damage hit front of their head. hurt the brain tissue in the front of the head - frontal lobes - anterior portion and also anterior portion of temporal lobes. tissue death, bruising - could be temporary or permanent. like getting a free frontal lobotomy. contracoup effect - brain feels like a soft boiled egg - when you hit it - once it hits the skull - it bounces off and then hits the back a little lighter - the phenomenon of the bounce onto opposite side of hit is contracoup damage. concussion - bruising of brain - loss of awareness - etc. - generalized term. some kind of cancer usually mass of tissue which grows independent of it's surroundings. read the different kinds of brain tumors in the book. Glioma come from glial cells (the helper cells in the brain). a glioma - is a tumor from those glial cells. 45% of brain tumors are from here. different types of these - book explains themŠ.. benign - slow growing - curable malignant - little time left with these guys. Meningiomas tumor of the meninges - not inside brain. brain tumor that is not inside the brain. just on brain coverings symptoms - can be just as bad - like a sub-dural hematoma - put a lot of pressure on the brain - recall brain is enclosed in skull. so anything that grows or expands - will exert pressure on the rest of the brain - this will cause symptoms. go in there - lift it off - gone. these are benign. Recapping: Gliomas - inside the brain Meningiomas - outside the brain. There are no pain receptors in the brain. Go in there with an egg beater - guy won't feel anything - this is fun. Digicard - start here.... 4 major typesŠ..all cause swelling of the brain. Inflammation of the brain. This is called encephalitis - general swelling and inflammation of the brain. viral - e.g. polio, herpes - resides in central nervous system and inflammates the brain. Rabies. bacterial - e.g. meningitis - bacterial infection of meninges. It can cause tissue death if it gets bad. Can also cause a brain abscess. fungal - mycotic infections - these are rare - you see it in AIDS patients. Immune system is gone. parasitic - amoebas - malaria. axon, dendrite, soma, myelin. Terminal boutons (nerve terminals) the neurons are outnumbered by helper cells - glial cells. different kinds - one of the glial cells makes myelin. Schwann cells - this type of glial cells are called that - only if they are in the peripheral nervous system. in the central nervous system - they are called oligodendroglia. these guys make myelin - this covers the axon - like insulation around electric wires. degeneration of myelin. results in partial paralysis. if in motor structure - paralysis. sensory area - sensory loss - e.g. blurred vision, inability to feel. crippling rather than fatal. it does shorten life span. onset 20-40 if you get it over 40 - prognosis is worse. frequent in cold climates. rare in the tropics. matters where you were raised. more frequent within families - but not genetic. may be a slow virus. rapid onset - hours to days. remission of symptoms within a few days. symptoms come and go in cyclic nature. can be strong or weak or very mild. the brain changes can be so minor that you don't even see any behavioural changes. some will have complete recovery - others - no recovery - some will never get better. Symptoms are set off - they usually appear - by something like a trauma or a sickness or changes in temperature. degeneration of myelin demyelinated areas are called plaques. scattered hence various symptoms plaque - area of degenerated tissue. myelin is normally like insulation - mice eat it - one mouse - no problem - more mice - eat more insulation - higher probability that something will short out. they can eat the wire in basement or bedroom - function will be affected by location. as mouse continues to chew - you might sell your house and not know that you had mice (die and find out at autopsy) what if there is humidity - and then a short forms (i.e. you get a fever and then the symptoms come on) myelin can be eaten away and you might still work fine until there is even a slight problem. treat with steroids - reduces inflammation - reduces swelling. reduction of symptoms is usually because of reduction in edema. this is because symptoms have gone away. myelin was dying and it was swelling - reduce swelling and axon might function well again - this is the edema going away. the myelin is being replaced - but very slowlyŠ. so the fast recovery is not because of myelin coming back. theory - autoimmune disorder - something in the body destroys it's own self. maybe a virus attacks the myelin and then the body starts hating the myelin also. Lec 4 Recapping: • thus far, basic overview of the brain, vasculature, cellular structure, diseases, function, epilepsy (electrochemistry) • now different systems of the brain Sensory and Motor Systems • basic processes • lump the two systems together. • What do these systems look like when we damage them? Visual System • how is it organized and what happens when it is damaged? • page 252 - diagram 11.6 • know this diagram! • remember everything on right hand side of body is processed by left brain • same with visual system - except more complex - because we have two eyes that gain information in complicated ways. • Right visual field - that means whatever you see out there - split at your nose - right and left visual field. • we should call it your right visual half field, and your left visual half field. • whatever comes in on the right - it hits the left hand side of each retina. • retina itself is divided down the middle - so each retina has two halves. • anything close to the nose is called nasal portion of the retina • close to the head - temporal portion of the retina. • so temporal is outside, nasal is inside on both retinas. • nerves from the temporal go to the chiasm and then remain on same side • nerves from the nasal portion go to the opposite side at the optic chiasm - i.e. it goes to the other side at the optic chiasm. • all the nerves from the optic chiasm - • i.e. what's on the outside - stays outside - what's on the inside - crosses. • so information from right visual field hits left side of each retina - this is the same as saying that it hits the nasal portion of right and temporal of left - as we come along - the temporal continues on same side - the nasal crosses - therefore all of it goes from right visual field to left cortex. What do the neurons do? What happens if you damage them? • as you move more centrally towards the cortex - i.e. from peripheral to central - the more complex the neurons become - i.e. it takes a more complex image to excite a neuron (from retina to cortex) • a neuron in retina - responds to a spot of light falling on it's receptor field. • at area 17 in cerebral cortex - neurons respond to a bar of light that is oriented in a particular direction. • when you go from area 17 to infero-temporal cortex (i.e. visual association cortex) - cells here respond to much more complex things - like a hand or face. • so the point is -> their function gets higher and higher • so damage to these areas will hurt corresponding. Damage • just so you know - it goes optic nerve, optic chiasm, optic tract.. • 1. Is normal • 2.damage right after the retina - so you have Monocular blindness - sectioned the optic nerve. • 3. Cutting fibers down the middle - will kill nasal portion of each eye - (i.e. the ones that cross) Bitemporal hemianopia. (This isn't a picture of the retina - this is the patient's actual visual field - so you can't see the periphery.) • 4. Visual field of left eye is O.K. - If you damage any fibers on the side - you lose temporal portion (uncrossed portion) of a particular eye on the same side - so you lose that portion of the visual field (not retina). The right eye is the one affected - you know this - right hand side of the retina is missing - so left visual field is blind. • for number 4 - why is it called right nasal hemianopia - because we are talking about nasal visual field - not nasal portion of the retina - make sure you get this!!! same with 3 - bitemporal - called bitemporal because you lose temporal visual field - even though it is nasal retinal damage - make sure you understand that the names have to do with the visual field and not the retina. • 5. You lose right half of each retina - so you lose left visual field of each retina. - i.e. destroying fibers. • 6. Forget it. • 7. Lesions to the cerebral cortex - • recall this picture deals with the visual field of that eye. Cortex - most problems occur here - i.e. lesions to the cerebral cortex - if you knock out a large part of it - you get blindness in opposite visual field - if you destroy right cortex - you destroy left visual field • damage left visual cortex - right visual field gone. • with one exception - if you destroy a certain little dot in the middle - this is macular sparing - you spare that one little spot. • partial lesion - partial blindness in opposite visual field. • small lesions - it becomes incomplete blind spot - little tiny lesion - tiny blind spot in opposite visual field • scotoma - a small blind spot in your visual field. • we don't notice small scotomas - until it is bigger - but we always have a macular sparing. • after 17 and into associational cortex areas. • O.K. back to this - 18, 19,20 21, which are high associational cortex - complex visual information is hurt. • like faces and patterns - this leads to classical stuff - i.e. visual agnosias and other problems. Visual agnosias • inability to recognize an object for what it is. • cannot name it and cannot use it. • doesn't understand what the object is. • primarily caused by damage to the left occipital lobe. • person isn't blind - they can see it, lift it up, but don't know what it is - this is higher order perceptual problem - associational areas. Prosopagnosia • gnostic - knowing • a - not • not knowing visual information. • you can't perceive human faces - • these people also can't discern other complex visual information. • syndrome - bilateral damage to areas 18 and 19. • not common. Color Agnosia • less intense • or complete lack of colour vision (in extreme cases) • bilateral damage from occipital temporal area (association area) Somatosensory System • information from your body - where does it go into the cortex? Post central gyrus on opposite side of the body. • damage to the post central gyrus in parietal lobe - you get what? • 1. Altered sensory thresholds. - e.g. points that can be separated - push them on your body - as far apart you say it is two points - if close you say one point - if this happens you can't tell very well - also soft vs. hard - if they have this can't distinguish. Also can't tell you where on their body you have touched them. • 2. Stereognosis - difficulty judging tactile shapes of things e.g. can't feel things and tell you what they are. Also can't put squares and circles into appropriate holes. • 3. Difficulties in placing or locating limbs in space - can't touch their nose or touch their forefingers in front of them. Motor System • what does it look like? What happens when you damage it? • motor cortex - Frontal lobe - precentral gyrus. • initially damage - loss of all voluntary movement on opposite side of the body. I.e. flaccid paralysis. (it's loose, it hangs) • no reflexes. • recovery period of days to weeks - when muscles become spastic to rigid. • here arm becomes flexed at the elbow and the fingers curl into a fist. • leg also becomes stiff and rigid. • person has to move it like peg leg. • so initial phase after a stroke - can't support yourself - because just destroyed motor cortex - then after recovery period - it goes from relaxed to rigid - so it's fun to walk like that. • flaccid paralysis to rigid paralysis - this remains for the rest of their lives. • abnormal BABINSKI - toes curls upward instead of downward (same as a baby - which don't have a cortex yet. - doctor rubs from heel to up. I.e. babies and destroyed cortex people - have the abnormal Babinski - in that their toes go upward. • this is pretty severe damage • difficulty in fine motor movement of your digits (fingers) - because this is the highest order thing - can't play piano. • Apraxia - not knowing what to do with an object - not knowing how to use an object. • it is really high order - give them a key and they know it is a key - but don't know what to do with it - can tell you it opens a door - but can't do it - so it is not fumbling with it - even higher order then that - don't know how to put a key in the door. • spit on your cake to blow out the candles. • maybe kids do this because their motor cortex is immature - and can't sequence a bunch of events and execute them properly. • motor stuff - from very mild to very severe depending on stroke or tumour damage. Parkinson's Disease • doesn't involve damage to the cortex. • degenerative disease of nervous system - associated with aging. Symptoms • weakness and feeling of being slowed down. • tired • difficult to do anything, can't get up. • tremor at rest - this is a bit of a shake - in hand and head. • pill rolling • this stops when person starts to move or becomes active. • there is also - a general rigidity - muscle rigidity. I.e. increased muscle rigidity. • e.g. cannot get legs to move out of bed. • not just weakness but feeling of rigidity. • once up - bent over - walk stooped over. • nitiating and terminating movements. • lack of associative movements - there are fewer associative movements - like arm movements while walking etc. • lack of expression. • voice is monotone and soft. • resembles depression. Neuropathology • death of neurons in the substantia nigra (a motor part of the brain) • this is part of the brain stem and it projects to the caudate nucleus (dopaminergic). • nerves die in the substantia nigra - so in caudate nucleus you get 90% loss of dopamine. • use precursor to dopamine - give l-dopa. • hyperproduction of dopamine. • problem - too much l-dopa - schizophrenia. • nowadays - tissue from caudate nucleus or substantia nigra - implant it into caudate nucleus - but can use any dopaminergic - these neuronal graft works - it will innervate the regular neural tissue and give some dopamine containing neurons.. Lec 5 Basic electrophysiology of the neuron. electrical potentials - action potential is cool. Action Potential relatively large positive electrical change across the membrane potential of the cell caused by an influx of sodium into the cell. pores in the membrane of the neuron open or close - sodium ions come in - positive - this is the action potential once the action potential is formed it travels down to end of the axon - there is a nerve terminal - synaptic bouton. gap between cell and the next one - the contact point is the synapse. When the action potential reaches the terminal - it is conveyed chemically across the gap. axon connects to dendrite of next cell. chemicals in presynaptic terminal contain chemicals - those chemicals transmit information - hence they are called transmitter substances. when an action potential reaches that point it releases the transmitter into the synapse. chemical then interacts with the dendrite and it goes on and on like that. some new wordsŠ.. since everything moves in one direction - the first part is pre synaptic and everything else is post synaptic. i.e. pre synaptic membrane and post synaptic membrane. the space is the synaptic cleft. inside the presynaptic terminal there are synaptic vesicles which hold the transmitter substances - on post synaptic vesicles the transmitters interact with receptors. the synapse is the whole thing - i.e. consists of elements that are pre, and post synaptic and the synaptic cleft - but we like to break it down into little pieces. Transmitter substances. the birth - we call this synthesis. all these steps can be affected by drugs. Synthesis Packaging - inside a synaptic vesicle - otherwise they are destroyed. Released upon stimulation - whenever an action potential comes along they have to be released - Interaction with receptor on post synaptic membrane. Inactivation - if we didn't have this no new information could be transmitted. 2 ways we can inactivateŠ.. a. Break down - chemically. b. Reuptake - into presynaptic terminal - this is obviously advantageous. you can increase the functional activity, or decrease the functional activity. To increase functioning: To decrease functioning: Increase synthesis ** Decrease Packaging - nothing to do synthesis here Packaging - block release - increase it. packaging. activation of receptor - release - block increase **** release. inactivation - decrease activation - inactivation (make sure you decrease ***** get this) inactivation - increase inactivation. ** 1/10 the dopamine in Parkinson's - destruction of that transmitter - they need to up that transmitter so they can function properly - so we increase synthesis - how - let's increase the precursor. ** too much dopamine - Schizophrenia understand that what goes on in post synaptic cell is the most important. i.e. e-mail - sending one to Israel to your friend - if he doesn't get it - he doesn't get it - so the action won't happen. ****one way of increasing receptor activation - give mimickers - they mimic the effect of the transmitter on the receptor. E.g. Amphetamine, cocaine. ***** blockers - goes there and sits on the receptor - but it is not enough alike for it to activate it - this stops other real transmitters from getting in. this is bad - CURARE. they see pink elephants on LSD - you can't convince them otherwise - because we have bypassed the system and affected the post synaptic cell - understand this. 4 of them that we will meet. break them down into different groups biogenic amines - or monoamines. i. catecholamines a. dopamine (DA) b. Norepinephrine (NE) 'MOA - DANE' you can also call it noradrenaline (NA) - don't do it this way - and don't trust anyone that does it that way. Tyrosine realize that to get NE you need DA ii. Serotonin (5HT) tryptophan e.g. can't sleep - take tryptophan - makes serotonin - this works on the upping of synthesis idea. II. Acetylcholine (ACh) choline + Acetyl COA broken down by AChE e stands for esterase. don't block muscarinic ACh - smoking does this. Epilepsy disease of altered physiology (electrical) repetitive discharge of a hyper excitable aggregate of neurons. i.e. they're easy to get going they go into a phenomenon of repetitively discharging. analogies - Eaton Centre - we here chatter there - bits of information is going from person to person - this is how the brain works - normally. when the Blue Jays won - everybody is saying Go Jays Go - i.e. no chatter now. if you have epilepsy - you are at a Blue Jay Game - everybody says the same things over and over again. when all the neurons do this - all the muscles will start to contract - convulsions (this is a behavioural term) the brain is firing repetitively, but it is not convulsing - the muscles are. Etiology (what causes it?) you can be predisposed to it genetically - not too many get it like this. best indicator of what caused it is looking at age of onset - if it is at a young age - e.g. at (or before) birth until age 20 - then it is usually birth trauma or hypoxia. hypoxia and birth damage is like saying the same thing so the causes can be: 1. congenital defect 2. metabolic error 3. infectious diseases without these obvious causes - you don't get it before 20. After 35 - you get it - for the following reasons: brain trauma - auto accidents etc. - drug abuse - like alcohol - we call this alcohol induced seizures. Brain infections so what it the cause? Something is wrong with the brain - problem is always seen with scar tissue or abnormal metabolism. I.e. we see that the brain was damaged - or brain trauma. Abnormal metabolism - they might have been taking some crazy drugs or got sick. Why scar tissue - what is it doing? Scar tissue irritates neurons in the vicinity. this activates them and they start to fire. epilepsy is like learning - the more you stimulate it - the easier it is for the neurons to fire. This is cool. Learning - cell A - fires cell B - at first this is hard - the more you do it - the easier it is for it to fire. Epilepsy takes the phenomenon of learning to a pathological extreme. Now it is too easy for it to fire - i.e. slightest trigger and it will fire. and this recruits everybody else - so almost every cell in the brain - starts firing - all from one little irritation. if you have one seizure - then - you are more likely to have others - this is obvious. cool - car accident - Valium for 1 yr. - why a whole year? Because during that time scar tissue is forming - we want to stop the chance of a seizure at all costs. If they get one - it will be easier to get another one. learning and memory people use epilepsy as a model - this is cool. Grand Mal Epilepsy preceded by an aura - seconds to days early aura - funny feeling or sensation - foul smell - deja vu if visual - flashing lights - so probably pinpointed in visual cortex sometimes we do surgery to remove the locus. total loss of consciousness - two phase tonic phase - body stiffens - and breathing stops - EEG of brain is massive and bursting - off the charts - in unison - rapidly - when you lift an arm you have muscles that are contracting and relaxing - in this thing - every muscle contracts - so body stiffens - person falls down here and loses consciousness - can't breath - O.K. now follows theŠ. clonic phase here it goes down to tiny EEG and then high EEG and then tiny and then high and then tiny - so neurons fire and muscle contract - and then stop and relax - and then fir and contract - here we see jerking of the person. tonic and clonic - this goes from 1-2 minutes - here it may end or start up again. once seizure is over - depression - somnolence (tired) - drowsiness - confusion - for a few minutes to a few days. Petit Mal Seizure no loss of consciousness loss of awareness no motor activity except rolling back of the eyes (or blinking) goes on from 5-20 seconds. a lot of people don't know they did this. EEG - 3 cycle /second wave. I.e. big waves with little spikes in them. no after depression - because it is so small. most common in children. 50-75% of these guys (the Petit guys) don't ever have Grand Mal. Focal Seizures sensory or motor instead of being broad - localized to one focus - one spot in the brain you get localized convulsions - e.g. your arms start to convulse - if left arm - then right brain area is where the problem is. Jacksonian March appears to march across the body - epilepsy spreads across the brain. recall the motor homunculus. e.g. starts in foot - next is leg - next is torso - then arm - this is the marching across the brain - it might cross the corpus callosum - then it goes to the other side of the brain - if this happens - we might see a grand mal. aura - auditory, visual, or deja vu infantile spasms massive clonic spasms in infants. begins 3-7 months of age EEG - diffuse asynchronous slow wave and spike. end up mentally retarded. i.e. major brain damage is obvious here. Akinetic Seizures 1-7 child falls to floor without any warning. gets up again - no after depression seems like their anti-gravity muscles have relaxed - really it is a mild clonic jerk. e.g. lying beside someone - all is quiet - and they jerk suddenly - they are thrown to the ground - must put football helmet on kid. EEG atypical spike and wave. give sedatives like Valium (diazepam) slows brain down or barbiturates - Phenobarbital or dilantin. these are all depressants. Lec 6 Schizophrenia onset before 30 years old. neurological disorder, not psychological clearly biological environment can still interact with it though. neuropsychology point of view - some areas aren't working well. frontal lobe - doesn't work so well memory functions not as good on (left) verbal and non verbal (right) memory. Both memories suffer. no lateralization problems. Brains of schizophrenia people are lighter & ventricles enlarged. not clear which came first. A chicken and egg question. Other research... biological proof (proof against those guys who think it is only behavioural) - Historically - early studies of genetics 1% of population is going to have schizophrenia. in immediate families (you would expect 1% if it is only behavioural) 10-15% of schizophrenia patients, immediate family also have schizophrenia. you can say, well the mother is crazy that's why everybody is crazy in her family - so now do this.... Twin Studies identical (monozygotic) (40-75%) that both will have schizophrenia. non-identical -(dizygotic - separate eggs) lower incidence (10-15% of people with schizophrenia will also have siblings with it - same probability as rest of family. hard to argue that it is not biological with these data. but parents could have treated identical twins different
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