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Study Guide Exam 1 Biopsych

by: Emma Notetaker

Study Guide Exam 1 Biopsych NSCI 4510

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Emma Notetaker
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This comprehensive study guide includes both lecture notes and book notes.
Biological Psychology
Dr. Colombo
Biological Psychology, Colombo, biopsych, Psychology, Biology, neuroscience
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This 26 page Bundle was uploaded by Emma Notetaker on Friday February 12, 2016. The Bundle belongs to NSCI 4510 at Tulane University taught by Dr. Colombo in Spring 2016. Since its upload, it has received 249 views. For similar materials see Biological Psychology in Neuroscience/Psychology at Tulane University.

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Date Created: 02/12/16
Tuesday, January 12, 2016 Chapter 1 What is Biological Psychology? • biological psychology: biological bases of psychological processes and behavior (aka behavioral neuroscience) • neuroscience: study of the nervous system • brain produces behavior • behavior shapes brain (structurally - thinking about one thing over and over again creates network circuitry) 5 viewpoints • 1. describing behavior • can be described by different criteria (detailed acts OR results OR functions) • structural • functional • 2. studying evolution of behavior • comparing species to learn evolution 2 emphases: • • 1. continuity of behavior and biological processes due to common ancestry • 2. species-specific differences in behavior that evolved as adaptions • nature is conservative (conserved features from common ancestor) • 3. development of behavior and biological characteristics over lifespan • ontogeny: process by which individual changes in the course of its lifetime (aging process) • 4. biological mechanisms of behavior • underlie all behavior • regard organism as machine • 5. applications of biological psych (to human problems) • improving human condition (curing diseases, etc.) • each perspective can be applied to kinds of behavior (ex: sexual, learning/memory, and language/communication) 3 Approaches Relate Brain and Behavior • 1. somatic intervention most common • • alter structure or function to see how behavior will change • behavior is dependent outcome, body is independent variable • ex: administer hormones, stimulate brain region, cut connections • 2. behavioral intervention • intervention in behavior looking for resulting changes in the body structure or function • behavior is independent variable, body is dependent outcome ex: put male in presence of female, present visual stimulus, give training • • 3. correlation • finding the extent to which a given body measure varies with given behavioral measure • measuring both behavior and body 1 Tuesday, January 12, 2016 • no independent or dependent variables Neuroplasticity: Behavior can Change the Brain • neuroplasticity: ability to be changed by the environment and experience • other people can influence the physical structure of the brain (socially) • biological and social factors interact and affect each other continuously Levels of Analysis: scope of experimental approaches • reductionism: breaking system down into increasingly smaller parts in order to understand it levels (higher to lower) • • social • organ • neural system • brain region • circuit • cellular • synaptic • molecular • can be similar at lower levels without being the same at higher levels • approaches of study are different for each level History of Brain Research • used to believe mental capacities in the heart • Descartes related mind to body - pineal gland • dualism: notion that mind is subject to only spiritual interactions while body is subject only to material interactions • phrenolgy: bumps on the skull reflect enlargements of brain regions responsible for certain behavior • modern biopsych arose in 20th century • consciousness: state of awareness • very misunderstood 2 Tuesday, January 19, 2016 Week 2 Cellular Neuroanatomy 1 • wide variety of neurons • sensory neurons: rich arbor with lots of dendrites • motor neurons are the largest LONG axons that have to project to brain • • arborization spread of where the information is received • depends of spread of where information is received • globus pallidus neuron: part of basal ganglia, integration preparation for motor • interneurons: localized processing (small axons) • structural classification: multipolar: all motor neurons, most interneurons • • many processes • bipolar: 2 processes off cell body • association with sensory processing (ex: olfactory) • unipolar: 1 process off cell body (which bifurcates) • uncommon in developed neurons (mostly in embryo) sensory • • structural divisions: • 1. input zone: dendrites • 2. integration: soma • 3. conduction zone: axon • 4. output zone: axon terminals (synaptic boutons) neuroanatomical methods: • • Golgi stain: fill WHOLE cell • fills only a small number of cells • filling with fluorescent molecules • Nissl stains: outline ALL cell bodies (dyes attracted to RNA inside cell) • autoradiography: cells manipulated into taking photographs of themselves radioactivity emitted by labeled drug • • immunohistochemistry: brain slices exposed to antibodies selective for particular protein, then rinsed off and chemicals make antibodies visible • in situ hybridaztion: radioactively labeled nucleic acid with gene of interest turned on • can reveal immediate early genes - identity regions active in behavior performed shortly before synapses: • • dendodendritic • axodendritic • axoextracellular: terminal with NO specific target - neurotransmitters go into ECF • axon stops without making synaptic connection • axosomatic **axosynaptic** • • ends on ANOTHER TERMINAL • VERY important modulation (changing another connection by increasing or decreasing strength of synapse) • emotions are example of modulation in the limbic system 1 Tuesday, January 19, 2016 • axoaxonic • axosecretory: terminal ends on tiny blood vessels to secrete nt directly into blood neurons are very plastic - change as a result of experience • • in order to change, must build new things in soma • axonal transport: • rapid transmission of signals OUTSIDE the axon, slow of substances inside • neuron parts • plasma membrane: phospholipid bilayer each layer has polar phosphate head (hydrophilic) and nonpolar HC tail (hydrophobic) • • anything water soluble CANNOT cross - must interact on surface • anything lipid soluble can pass through, so receptors for these are inside • scaffolding (cytoskeleton): • microfilamentes, neurofilaments • microtubules: cytoskeleton AND transport microtububle associated proteins (MAP) - ex: Tau (involved in Alzheimers) • • mitochondria: energy production • makes ATP from pyruvic acid (fat, sugar and protein) • aerobic respiration: difficult process, sometimes not best for us • oxidative stress • involved in cell death/apoptosis Golgi apparatus: packaging, delivery in vesicles • • molecules interact biochemically • vesicles interact with other molecules in transportation (easier to move vesicles vs. molecules) • transcription: in nucleus, code is mRNA • copy of original genes made with mRNA transcript • plasticity: gene transcription and making new proteins • transcription factors: signals initiated in membrane that go to interact with genes • responsive to environment • function is to increase or decrease production of different proteins • translation into proteins • in ribosomes on ER and on free ribosomes • ribosomes associate with transcript and call in amino acids • assemble protein strands • proteins: • SHAPE important • primary sequence: amino acids • secondary: alpha helix • tertiary: protein folding • way that it folds determines what parts are available to react (those on the outside - insides tucked away and can’t react until shape change) • nt binding can cause this change • quaternary: # of tertiary molecules come together to form protein complex (made up of multiple subunits) • transport: • motor proteins: • dynein: retrograde (recycling molecules - from axon to dendrites) • kinesin: anterograde (forward) • motor proteins travel along filaments and bring molecules and vesicles 2 Tuesday, January 19, 2016 • microtubules are bigger than filaments • notes on real pictures: perikaryon: substance within neuron • • nissile substance = ER • calcium sequestered in ER - important for initiating plasticity • tightly controlled • turns things ON • sections in 2D axon x-section • • myelin sheath: dark rings around axons • dots inside: filaments • small circles are microtubules • gap between = node of Ranvier • tubules localized in astrocyte, spread randomly in axon dendrite • • spines: area of synaptic contact • retarded infant spines are longer, more spindly compared to the normal short/stout • synaptic contacts all around dendrites • dark circles are mitochondria • can sometimes tell type of nt by shape of vessel (rounder = excitatory, flatter/ asymmetrical = inhibitory) • **formation AND elimination of dendritic spines contribute to learning** —> reshaping brain • 2-photon microscopy: high resolution technique • chronically implant window in skull to view dendrites in cortex (can’t go deeper than cortex) • mouse alive, view dendrites for period of time • looks at experience-dependent change over time • behavioral intervention: mice trained to take spaghetti through slot (have to turn it to grab) • motor training • day 1: immediate formation of spines in contralateral motor cortex (same amount of elimination compared to controls) • over time, more spines formed AND eliminated in the mice that learned and were successful • ONLY occurs in contralateral motor cortex (not sensory) • if no learning, spines stayed the same Cellular Neuroanatomy 2 • glia: divide throughout lifespan (always making more glia) • DON’T form synapses • make blood brain barrier • regulate ion concentration in ECF • glue signaling capabilities • • take up neurotransmitters to be recycled (convert into new nt) • form many types of tumor by swelling (edema) • the brain and CNS is a tube (ventricles, spinal cord, cerebral aqueducts, etc.) • lining of tube: ependymal cells • outer layer: meninges 3 Tuesday, January 19, 2016 • glia limitans • blood vessels made of endothelial cells (line vessels) • • pericytes wrap around endothelial cells • these are contractile, contribute to the tone of blood vessels and regulate blood pressure • blood brain barrier: NOT a physical covering of the brain • tons of capillaries - every cell only microns away from a capillary ending every capillary has end feet processes on it (THESE astrocytic end feet ARE the BBB • between capillaries and brain) • CNS • macroglia • astrocytes • form end feet which surround (completely) capillaries, nodes of Ranvier, dendritic spines • feet: glia limitans • entire vessels covered by these • types: • fibrous - white matter (more skinny strands) • protoplasmic - gray matter (more clumpy) regulate blood flow to provide more supplies to neurons when they are active • • monitor activity of nearby synapses • take up neurotransmitters • active coupling of neurotransmitter metabolism between neurons and astrocytes: • glutamate converted by astrocytes to glutamine (precursor), then glutamine goes out and is synthesized into glutamate (and sometimes GABA afterwards) • ONLY astrocytes hold the enzyme to convert to glutamine so recycling only occurs here • oligodendrocytes: myelinate neurons in CNS • one wraps several axons • synthesize no-go protein so nerve cells DO NOT regenerate in CNS • **can put Schwann cells in CNS to regrow nerves but they will not create functional growth; leads to unregulated plasticity (cancer) • microglia: immune response • injury response and inflammation • swelling is the microglia ingesting debris • cannot suck out the debris because ingested by these glia - needs more room • also ingest dying cells (ex: oligodendrocyte) • different levels of pathology: • small, sparse: diseased cerebral cortex • gross pathology: thicker processes • converting into phage: consuming brain material (phagocytosis) —> now have become phagocytic macrophages • ependymal: inner lining of fluid systems (ex: cavities, central canal) • PNS • satellite • Schwann: wrap one axon • nerve regeneration does occur here • interneurons: neither sensory nor motor 4 Tuesday, January 19, 2016 • give GRADED response as opposed to all or none (categorical) • modulated response 5 Sunday, January 24, 2016 Week 3 Systems Neuroscience I • Broadmann’s areas: 47 areas of the brain based on the cell types (cytoarchitecture) • Broadman used Nissl stains (which stain the endoplasmic reticulum - cell bodies) on the cortex in order to see where different cell types cluster 1, 2, 3: primary somatosensory areas (postcentral) • • 4: primary motor (precentral) • 8: frontal eye field • 17: primary visual cortex (occipital lobe) • 18/19: visual association cortices (extrastriate areas) • 41/42: superior temporal gyrus (audition) 43: inferior frontal and insula (gustatory - taste) • • 44: pars opercularis (part of Broca’s area and inferior frontal gyrus) • 47: pars orbitalis (part of inferior frontal gyrus) • Paul McLane: triune brain theory • we have an evolved brain that has 3 parts, which causes competition between the different areas (why sometimes we can’t decide whether to make the emotional or the rational decision) • some invest more thought to one area, and because our brains are plastic these connections are enhanced • 3 brains: • 1. reptilian brain - only has brainstem and basal ganglia • habits and motor functions 2. paleomammalian: emotion (developed limbic system) • • 3. neomammalian: rational decisions (neocortex) • association cortices: mostly prefrontal and posterior parietal • information (sensory) goes to sensory processing areas (most of Broadmann’s) and then brought together in these association areas • multiple sensory inputs, stored info, memory of past experiences horizontal brain section: • • 2 large nuclei visible • thalamus: posterior to basal ganglia • basal ganglia: anterior to thalamus • gray matter: cortex • white matter: axonal fiber systems brain development: • • starts off as neural tube • tube forms 3 bumps, which become: • prosencephalon: forebrain • telencephalon • isocortex or neocortex basal ganglia • • limbic system • diencephalon • hypothalamus • thalamus 1 Sunday, January 24, 2016 • mesencephalon: midbrain (STAYS midbrain, doesn’t develop after this point) • rhombencephalon: hindbrain metencephalon • • cerebellum • pons • myelencephalon • medulla • fiber tracts: association tracts: connect cortex to cortex in same hemisphere • • cingulum: in cingulate gyrus • arcuate fasciculus: language functions (connections between speech sound areas and motor output areas) • uncinate fasciculus • commissures: connects cortex in different hemispheres corpus callosum: continuous fibers • • projection fibers: connect subcortical to cortical levels • ascending and descending tracts • motor output and sensory input • ventricular system: • acts as shock absorber for brain and medium of exchange filled with cerebrospinal fluid (CSF) • • continues up from central canal of spinal cord • bottom (closest to spinal cord) - 4th ventricle (in midline) • 4th ventricle becomes cerebral aqueduct, which connects to 3rd ventricle • 3rd ventricle splits into the 2 lateral ventricles • these project to all lobes • lined with choroid plexus (which secretes CSF) • vascular system: • carotid arteries: go up the left and right sides of the neck (front) • branch into external and internal carotid arteries • internal carotid artery: branches into anterior and middle cerebral arteries (supply about 2/3 or cerebrum) • connected to the vertebral arteries via the posterior communicating artery • connects to the posterior cerebral artery • vertebral arteries (left and right) fuse to form basilar artery • on the back of the neck • branches into the two posterior cerebral arteries - supplies about 1/3 of cerebrum • circle of willis - structure at base of brain formed by joining carotid and basilar arteries • blood supply made of arteries going TO the brain • supply to the whole brain from the 3 cerebral arteries • strokes: vascular damage • 3 areas on the circle of willis account for 90% of strokes (these are mostly where larger arteries become smaller vessels, which may account for the issues) • junction of cerebral and anterior communicating artery: 30% • junction of carotid and anterior/middle cerebral arteries: 30% • branches off the middle cerebral artery: 30% 2 Sunday, January 24, 2016 Systems Neuroscience II basal ganglia: linked to thalamus in the base of the brain • • components: • caudate nucleus (top - similar arc to corpus callosum) • globus pallidus/putamen (form the lentiform nucleus) • under the caudate nucleus (ventral to caudate) • putamen is lateral globus pallidus is medial • • amygdala - almond-shaped, ventral • internal capsule: right under caudate nucleus, above putamen • fiber tract connecting subcortical white matter • substantia nigra - cluster of cells that produce dopamine • right above pons • outside red nucleus • info from all over the cortex to striatum/globus pallidus then back to the cortex • reciprocal loops throughout the basal ganglia • can be partially targeted by OCD, repeated pattern • known mostly as motor system • also cognition • connections: look at slide 5 • feedback circuits - integrate sensory and motor in basal ganglia • afferents: • 1. corticostriate (cortex to striatum) • circuit, reciprocal (compared to ascending sensory feedback) • caudate to globus pallidus to thalamus • back to cortex • thalamostriate (thalamus to striatum) • 2. nigrostriatal (substantia nigra to striatum) • dopamine pathways • subtantia nigra to globus pallidus, putamen, caudate to thlamus • feedback back to substantial nigra (GABAergic) • efferents: • pallidotegmental • pallidothalamic • lenticular fasciculus • ansa lenticular • pallidonigral • thalamocortical • limbic system: curves through each hemisphere along basal ganglia • emotion and learning • components: • amygdala: emotional regulation and odor perception • hippocampus/fornix: learning and memory • stimulus and stimulus associations • parahippocampal gyrus: higher order sensory information and associations • cingulate gyrus: cognitive functions (attention) • olfactory bulb: smell • near hypothalamus: motivated behaviors emotional/visceral brain 3 Sunday, January 24, 2016 • inputs from all sensory modalities • outputs: sympathetic activation • • motor • endocrine • visceral • somatic • lesions can cause a type of docility imaging techniques: • • angiography: xray image of head taken after blood vessels filled with radiopaque dye through catheter • CT scans: x-ray absorption at several positions around the head • medium-resolution images • cheaper MRI: higher resolution, reveals subtle changes • • magnetic energy generates images to reveal structural details • protons in brain tissues line up in parallel • patients not exposed to xrays • PET: track radioactive substances to produce images of brain activity • radioactive chemical infected, and detectors find destinations expensive, invasive • • fMRI: reasonable speed and good spatial resolution • detects changes in blood flow to see which areas are active • subtraction technique • visualize functional brain activity • DTI (diffusion tensor imaging) - diffusion of water within tissue, lets you see orientation of fiber tracts within brain • optical imaging: visualize brain activity in which near-IR light is passed through scalp and skull • transcranial magnetic stimualtion: stimulation of cortical neurons through application of strong magnetic fields • magnetoencephalography: • good temporal resolution • measures magnetic fields produced by active neurons to see where brain is active • speed-accuracy trade off: high resolution is usually slower • cerebral cortex • 6 layers • layers alternate between granule cells and pyramidal cells • I - few cell bodies (almost no neurons) • glial cells • molecular layer • II: external, granular layer • dendrites extend to layer I • small pyramidal • III: external pyramidal layer • dendrites extend to layer II • medium to large • IV: internal granular layer • many neurons with many cell bodies 4 Sunday, January 24, 2016 • HIGH concentration of stellate cells • special processing direct input from thalamus • • V: internal pyramidal layer • medium • large cells • many neurons with many cell bodies • large pyramidal VI: multiform layer • • spindly shaped neuron • fusiform cells • stellate cells —> golgi II cells (local axons, process nearby) • golgi I cells: project long distances • allocortex: tissues with 3 layers or unaltered organization pyramidal cells: most prominent neuron in cerebral cortex • • in layers III and IV • apical and basal dendrites • cortical columns: vertical columns that constitute the basic organization of the neocortex • most synaptic interconnections are vertical - information processing units • nerves divided into 3 systems spinal • • 31 pairs • dorsal roots are sensory, ventral roots are motor • 8 cervical (neck) • 12 thoracic - trunk • 5 lumbar - lower back • 5 sacral - pelvic • 1 coccygeal - bottom • cranial • 12 pairs • some sensory AND motor • look at relative/anterior position in diagram • blue mostly sensory, pink/red mostly motor • 1: olfactory - smell • 2: optic - vision • 3. oculomotor - muscles that move the eyes • 4. trochlear - muscles that move the eyes • 5: abducens - muscles that move the eyes • 6. trigeminal - face, sinuses, teeth, movement of jaw • 7. facial - tongue, soft palate, muscles of face • 8. vestibulocochlear - inner ear • 9. glossopharyngeal - tase/throat movement • 10. vagus - info from internal organs/their movement • 11.spinal accessory - neck muscles • 12. hypoglossal - tongue muscles • sensory and motor on head and neck • never join the spinal cord • locations: • anterior of brain: 1, 2 5 Sunday, January 24, 2016 • midbrain: 3, 4 • pons: 5-8 medulla: 9-12 • • autonomic nervous system • preganglionic nerves: innervate ganglia (aggregates of neurons) • sympathetic: thoracic and lumbar • postganglionic: innervate the body • sympathetic: course throughout the boy sympathetic nerves: chain throughout body • • uses norepinephrine (accelerates activity) • parasympathetic: dispersed throughout • uses ACh (slows things down) • enteric: local network of sensory and motor neurons that regulates the functioning of the gut brain features: • • gyri: tissue ridges • sulci: furrows separating gyri • white matter: fiber tracts • gray matter: cell bodies and dendrites • CNS: nuclei - groups of neurons • • tracts - bundles of axons • PNS: • ganglia: groups of neurons • nerves: groups of axons • diencephalon: • thalamus: cluster of nuclei acting as a switchbox for directing sensory input • hypothalamus: vital functions • hunger/thirst • temperature • sex • controls pituitary gland - hormonal system regulation • midbrain: • tectum: • superior colliculi - visual • inferior colliculi - auditory • substantia nigra - release dopamine • red nucleus - communicates with motor neurons • reticular formation - sleep and arousal • cerebellum: convoluted for more surface area • motor coordination and control • cognition • 3 layers • Purkinje cells: fan shaped dendritic patterns • granule cells: small neurons • molecular layer: consisting of parallel fibers • pons: motor control and sensory • medulla: transition from brain to spinal cord • regulates breathing and heart rate 6 Sunday, January 24, 2016 • meninges protect brain: • dura mater-outer • pia mater - inner (on surface of brain) arachnoid: surrounds brain in bath of cerebrospinal fluid • 7 Monday, February 1, 2016 Week 4 Changes to Systems Neuroscience Slideshow • cranial nerves: I: olfactory (sensory) - smell • • II: optic sensory) - vision • III: oculomotor (motor) - most eye movement • IV: trochlear (motor) - moves eye • V: trigeminal (BOTH) • sensory: face sensation • motor: moves jaw for chewing • VI: abducens (motor) - abducts eye • VII: facial (BOTH) • sensory: taste • motor: facial expression • VIII: vestibulocochlear (sensory) - hearing and balance • IX: glossopharyngeal (BOTH) sensory: taste • • motor:gag reflex • X: vagus (BOTH) • sensory: parasympathetic innervation • motor: gag reflex • XI: accessory (motor) - shoulder shrug • XII: hypoglossal (motor) - swallowing and speech mnemonic devices: • • on old olympic towering tops a Fin and German viewed some hops • ooh, ooh, ooh, to touch and feel very good velvet. Such heaven! 1 Monday, February 1, 2016 • some say marry money but my brother says big brains matter more (s=sensory, m=motor, b=both) rostral midbrain: • • medial geniculate nucleus within thalamus • cerebral aqueduct in the middle • thalamus (bilateral) on the outsides • crus cerebri: outside substantia nigra • substantia nigra: involved in Parkinson’s, produces dopamine and sends it to the basal ganglia • pons: • trigeminal nerve comes off pons • sympathetic nervous system: activates organs • emergency: fight or flight • most ganglia are in cervical chain (a few others outside that) adaptive, acute stress response • • preganglionic nuclei: cholinergic (ACh) • postganglionic: noradrenergic (noradrenaline) • parasympathetic: • pre and postganglionic use ACh • NO chain - all ganglia near the organs Fiber Pathways • spinal cord: dorsal horns: sensory info (ascending) • • ventral horns: motor info (descending) • distinct butterfly shape (gray matter inside, white outside) • dorsal column medial lemniscus (aka posterior columns) • ascending, goes up dorsal spinal cord • somatosensory proprioceptive: body position in space • • receptors in joints (muscle spindles and Golgi tendon organs) • epicritic: fine touch, 2 point discrimination • encapsulated receptors (when squished, mechanically opens sodium channels to cause depolarization —> mechanically gated receptors) • Meissners Pacinian corpuscule • • perifollicular receptors • ganglia have extensions ending in receptor - these axons enter dorsal horn and ascend WITHOUT crossing in medulla • synapses and crosses in medulla • nucleus gracili: lower body nucleus cuneatus: upper body • • after crossing in medulla, fiber tract is called medial lemniscus • terminates in thalamus • lateral somatosensory cortex: upper body • medial cortex: lower body • lateral spinothalamic: 2 Monday, February 1, 2016 • goes up lateral spinal cord • ascending somatosensory - pain and temperature • • receptors are free nerve endings (fire AP in response to stimuli) • cell bodies in ganglia outside, terminate in skin • synapse/cross right away in spinal cord (may go up a few segments) - this allows for modulation • pain systems heavily modulated: morphine can inhibit neural conduction in various areas (because many descending axons around it) • ascends (branches and collaterals of off at all levels) • many opioids in periaqueductal gray • synapses in thalamus • tertiary neuron goes to post central gyrus • anterior spinothalamic: ascending • • somatosensory - protopathic touch • not well localized • associated with hairless skin • texture, itch, tickle • bilateral lesions cause less perceptual arousal, sensation receptors: Merkel’s discs • • synapses immediately in spinal cord and crosses • runs up spinal cord with branches along the way • ends in thalamus, which then goes to primary somatosensory cortex • goes up anterior half of spinal cord • corticospinal tract • descending - motor • voluntary movement • pyramidal motor system - runs through medullary pyramids • biggest motor pathway • newer evolutionarily (older is basal ganglia - extrapyramidal motor system) • cell bodies in motor cortex which descend to spinal cord and terminate (NO primary, secondary, tertiary neurons - just ONE big neuron) • descends to corona radiata • crosses in medullary pyramids (decussation of pyramids) • crus cerebri - fibers in midbrain • exits through anterior/ventral horn • terminates on muscle (on nicotinic, cholinergic receptors) • tectospinal: • evolutionarily older • starts in tectum of midbrain (roof) • home of superior colliculus - involved in visual following, eye reflexes, tracking • motor system • crosses immediately in midbrain • descends • synapses on interneurons (modulatory) • rubrospinal: • evolutionarily older • starts in red nucleus of midbrain 3 Monday, February 1, 2016 • motor system • modulates flexor muscles crosses immediately in midbrain • • descends • synapses on interneurons (modulatory) • alternate pathway from cerebrum • origins in cerebellum Development • domains: higher cognitive function • sensory integration • working memory (not long term) • inhibition • early stages • at 18 days: 3 cell layers (endoderm, mesoderm and ectoderm) • ectoderm forms neural plate (outer layer) • 20 days: neural groove develops (from uneven rates of cell division) 22 days: neural groove closes to make neural tube • • few days later: neural tube forms bumps (nervous system) - 3 bumps • forebrain, midbrain and hindbrain (form at rostral end) • dorsal root ganglion (groups of cell bodies - sensory) - form around developing spinal cord • **embryo until 10 weeks post-fertilization stages of development: (6) • • neurogenesis: mitotic division of non neuronal cells to produce neurons • nerve cells themselves DO NOT DIVIDE • cell giving rise to neurons are single layer along inner surface of tube - divide via mitosis • form ventricular zone - lines cerebral ventricles, ALL neurons and glial cells derived from here via mitosis • division produces progeny cells • 250000 cells/minute • central canal cells divide • sends out extensions/connections • retracts, divides, continues cells have specific “birthdate” • • cells sort themselves via cell-cell interactions • migration/aggregation (undifferentiated): movement of cells to establish distinct nerve cell populations • when dividing stops, extensions keep going which leads to migration (like climbing a rope) researchers can trace migration of C. elegans because they’re transparent • • move along radial glial cells, which act as guides • cell adhesion molecules (CAMs) protein on cell surface that guides cell migration and growing axons • may also help guide axons to regenerate if cut in adulthood • single file migration of nerve cell precursors 4 Monday, February 1, 2016 • differentiation: into distinctive types of many nerve cells/glial cells • based in local environment - once they reach their location, begin to express different genes • provides lots of opportunity for regeneration • put undifferentiated (eg: stem cells) in specific environments to regenerate • if cell shows characteristic independent of neighboring cells: cell-autonomous • embryonic: can be anything (totipotent) • other embryonic: pluripotent others: multipotent (restricted repertoire) • • induction: influence on one set of cells on the fate of their neighbors • regulation: adaptive response to early injury - developing cells compensate for missing/injured cells • synapse formation: establishment of synaptic connections • process outgrowth - growth of axons and dendrites synaptogenesis - proliferation of synapses • • at tips of axons and dendrites are growth cones • filopodia off and of growth cones: fine extensions • adhere to CAMs and contract to pull cone • CAMs are released by target nerve cells or other tissues • chemoattractants vs chemorepellants strong link between schizophrenia and synapse formation • • cell death • survival of the fittest (neural darwinism) - best at doing something stays, others are killed because of trophic factors —> programmed cell death • many neurons die early in development - chromosomes carry death genes (expressed only when cell undergoes apoptosis) • apoptosis regulated by cell-cell interactions • caspsases: family of proteases cutting up proteins and nuclear DNA • death gene regulation: • influx of calcium from outside cell and release of calcium from internal stores INCREASES calcium levels inside cell • calcium invades mitochondria - release of diablo protein • can be blocked by Bcl-2 proteins • Diablo binds to inhibitors of apoptosis proteins (IAPs) - no longer block capsases • capsases destroys proteins and DNA - can’t survive anymore • apoptosis occurs • neurotrophic factors: target derived chemicals acting as if they feed certain neurons to help them survive (if the neurons don’t get enough of these, they won’t survive) • nerve growth factor: affects growth of neurons in spinal ganglia and sympathetic ns system • access to NGF controls cell death • NGF-like factors: neurotrophin family • brain-derived neurotrophic factor (BDNF): keeps some classes alive • Process: • different neurotrophic factors introduced by different target cell groups • innervating neurons take up particular factors and transport them to soma • factors regulate expression of genes, which changes neuronal development • IF neuron gets enough neurotrophic factor - survives (if not, apoptosis) • matching of the size of target and the number of innervating neurons 5 Monday, February 1, 2016 • axons processes compete for neurotrophic factors too - active synapses more successful different experiences result in maintenance of different patterns of synaptic • connectivity • synapse rearrangement • see what works and what doesn’t (strengthen useful connections and get rid of useless ones) • unsuccessful synapses pruned back collaterals come for more precise wiring • • thinning process goes from caudal to rostral (forebrain last to develop) • neural activity may be main determination of which synapses kept • Factors affecting neural development: • intrinsic (genes) • chromosomal aberrations: down syndrome - extra chromosome 21 • • wide range of cognitive effects • fragile X - more common in males, long arm of X chromosome may break due to unstable DNA • wide range of cognitive effects • blocked normal elimination of synapses over 200 trinucleotide repeats • • single-gene effects: • phenylketonuria - protein metabolism disorder • absence of enzyme leads to toxic buildup of compounds which leads to disability • genetic • drosophila mutations • cerebellar mutations in mice (weaver and reeler) • extrinsic: • basic biological factors (issues with mother): • malnutrition • hypoxia - lack of oxygen • behavioral teratology: impairments produced by embryonic exposure to toxins/lack of nutrition • drugs/toxins: • fetal alcohol syndrome - changes facial structure, may not have corpus callossum • cell-cell interactions • induction directs differentiation: motoneurons induces by notochord • neurotrophic factors: NGF spares sympathetic neurons • thyroid hormone: deficiency causes intellectual disability • neural activity: • non-sensory-driven: eye segregation in layer 4 cortex before birth • sensory-driven (experience): ocular dominance outside layer 4 after birth, maternal bx affects gene methylation, increased IQ from childhood enrichment • epigenetics: study of factors affecting gene expression without making changes to the sequences of nucleotides • ex: identical mice put in different wombs of foster mothers • different behaviors due to different prenatal environments 6 Monday, February 1, 2016 • methylation: chemical modification of DNA that doesn’t affect nucleotide sequence but makes the gene less likely to be expressed can be affected by neuronal activity • • ex: pups with inattentive mothers leads to methylation of gene for gluticocorticoid receptor (stress) • experience influences: • amblyophia: reduced visual acuity NOT caused by optical or retinal impairments • sensitive period: organism can be affected by experience or treatment ocular dominance columns: in primary visual cortex (L, R, L, R, L, R) • • experience dependent cortical development in ocular dominance columns • A: normal • most cells respond to both equally • some on either side (bell curve) • most cells become binocular because both eyes stimulated B: monocular deprivation • • everything still works • cell mostly responds to input from the other side • can lead to blindness in that eye - has NO effect if deprivation after sensitive period • C: one eye deviated: cumbliophia • both eyes working but independently leads to poor depth perception • • eyes are not connected - cells will not be driven by BOTH eyes - independent • Hebbian plasticity: • Hebbian synapses: grow stronger or weaker depending on their effectiveness of driving the target cell • Hebb’s postulate: cell A keeps firing at cell B then some growth and metabolic change takes place in both such that A’s efficiency at firing B is increased • account for changes after monocular deprivation • deprived cells fire at random, which doesn’t cause postsynaptic cell to fire —> loss of ineffective inputs • mechanism of plasticity: location of plasticity its he synapse • How do cells know who to connect with? • chemoaffinity: chemical attraction —> YES (driving force) • each cell has a chemical identity that directs it to synapse on the proper target cell in development • projection fibers: project from one area to specific area on receiving cell • spots VERY localized with specific areas • retina reestablished the same pattern of connections to the tectum that was there before surgery, and brain interprets visual information as it did before • eye rotated 180 degrees after optic nerve cut - when recovered eyesight, behaved like image rotated 180 as well • gradients: areas project to gradients on the receiving cell • GRADIENTS are the mechanism • original chemical addresses created by matrix of two molecules at different concentrations • topography: relative location —> NO • gradients of chemicals - every intersection is unique • rat visual cortex: 32 fold increase 7 Monday, February 1, 2016 • in humans - decline of density of synapses after the first year of life (rts, continues to grow but then stays constant human cortex: various asymptotes • • layers of neurons - • a. newborn stains: no connections • b. 3 month old: grew a few connections • c. 2 year old: MANY connections • neurons in superior colliculus deeper are polymodal, superficial are unimodal • • unimodal (41%) • 25% visual • 11% auditory • 5% somatosensory • mutimodal: (49%) 29% visual/auditory • • 10% visual/somatosensory • 4% auditory/somatosensory • 6% ALL • 10% unresponsive • rate of myelination: as axons myelinate, connections go faster primary somatosensory • • 1. sensory myelinates FIRST • 2. motor myelinates after sensory • 3. association, prefrontal, inferior temporal go “online” later as a results of experience • multiple sclerosis: myelin is destroyed • myelin can be added throughout life • most intense form of myelination right after birth • infants as early as a few weeks old can integrate visual and tactile information • cortex still undeveloped - how do they do this sensory integration? • superior colliculus (older part of brain) allows for them to do this • electrophysiological responses - deep layers have cells responding to multiple modalities • does not require a long time for integration:new sensory integration system BUT old one still functions • multimodal sensory integration in colliculus - cortex still undeveloped • textured pacifier - integrate tactile integration • babies stared more at novel pacifier • autism: impaired social interactions and language • more common in males • perseverate: continue to repeat behavior (nodding head, finger movements) • avoid eye contact • reduced corpus callosum • frontal cortex less activated - cannot mimic facial/social cues • Asperger’s: retain language abilities (still impaired social cognitive processing) • brain continues to change as we get older • memory impairment correlates with shrinkage of hippocampus as we age • Betz cells in motor cortex start to decline in number around age 50 • inferior olive retains same amount of cells • Alzheimers: decline in cerebral metabolism 8 Monday, February 1, 2016 • form of senile dementia • can reduce risk with MORE use of the brain (NOT due to the brain wearing out) senile plaques in cortex, hippocampus and limbic system (formed by buildup of beta- • amyloid) • 3 enzymes (beta secretase, apolipoprotein and presenilin)that cleave amyloid precursor protein (APP) ineffective • neurofibrillary tangles - tau proteins form tangled array • cholinergic neurons in forebrain disappear 2 timescales to describe brain development: • • architect: genes carry basic plan that worked for generations • contractor: developing individual • uses general plans of architect to construct house • BUT requires judgement and interpretation • dorsolateral prefrontal cortex very important for higher cognitive functions (working memory, inhibition) • come online around 2 years of age • connectivity (shown by Golgi stains) is directly related to the functioning of this area • “A not B task” - Piaget (aka delayed match-to-sample) • subjects shown object, experimenter places object in one of 2 wells • delay - screen comes down or well is covered subject has to choose which one the object is in (working memory - to solve specific • problem) • in humans: ages 7-12 months, delay at which they can be successful increases • at 7, can only work with 2 second delay, but 12, can work with 12 seconds • monkeys develop at a much faster rate - can perform just as well as humans can at just a few months of age 9 Thursday, February 11, 2016 Week 5 Development (cont.) • humans around 2 years of age have decent inhibitory function (can wait to reach around object to get something they want) • before this, not a lot • other sensory functions can occur very early on due to alternate brain region that can accomplish task Aging 1900 - life expectancy was 47 years, only 4% of population over 65 • • 2011 - LE is 78.6, 14% of population over 65 • health span: making later years of life more enjoyable (want to extend this vs. old/infirm) • memory tests: memory declines with age (starts very early on - by 30s) • words recalled: • decline by 30s - rapid decline around it • by 80s - 55% recall words recognized • • much less rapid decline - relatively preserved • ALWAYS some older individuals who perform as well as the best young • average decline in elderly, but always individuals who have preserved cognitive function - NOT just a function of age • in aging, heterogeneity (different levels of cognitive function as we age) • shrinkage in hippocampus (in medial temporal lobe) strongly associated with aging • strategies using hippocampus (ex: spatial memory) may retain size of their hippocampus • can recover size of hippocampus - get it to grow again by exercising it • theories of aging (3): in normal humans (no pathology) • 1. cholinergic (Raymond Bartus) • cholinergic nuclei in basal forebrain in the brain • 1. are specific cholinergic dysfunctions in age-related cognitive loss? - do we see a differerence in cholinergic systems in young vs. old? • decreased cholineacetotransferase (ChAT - enzymesmakes ACh) in elderly with cognitive loss • decreased cholinergic neurons (measured by immunohistochemistry) in elderly with cognitive loss • evidence of deficits specific to cognitive loss • correlational study - discovered relation 2. does artificial disruption of cholinergic function in young subjects induce • impairments similar to those of elderly? • yes - scopalamine (ACh receptor antagonist) impairs memory • somatic intervention • 3. does replacement of ACh ameliorate age related impairment? • NO (not really - modest effects) • arecoline (muscarinic agonist - increases effects of ACh) has very modest effect early on, but barely slows rate of impairment 1 Thursday, February 11, 2016 • physostigmine (anticholinesterase - blocks breakdown of ACh) has very modest effect until a few years ago, ALLAlzheimers treatments were cholinergic • • when ACh replaced, cognitive impairment NOT replaced • 2. oxidative stress • cells use oxygen for energy production - consequence: stressors in cells cause them to die • reactive oxygen species (ROS): oxygen, ions, free radicals and peroxides highly reactive molecules - unpaired electrons in valence shells • • natural byproduct of aerobic respiration • we have involved mechanisms for deactivating ROS • BUT as we age, cells lose ability to deactivate these —> results in neuron loss/ cell death • nerve growth factor is protective against ROS superoxides (free radicals) • • defense against them (normal): • superoxide dismutase (SOD) converts them into hydrogen peroxide • catalase reduces H2O2 to water • damages (impaired defense): all lead to cell death • DNA damage in nucleus DNA damage in mitochondrion • • cell membrane damage • increased concentration of the defense enzymes increased lifespan in fruit flies AND extended healthy period of life (not just old age) • before 1990s - to count cells you counted cells on individual slides sections • BUT cells span multiple layers, so may count cells multiple times • scariology: construct cells in 3D - take cells in different planes • only count each cell ONCE • issues with theory: experiment showed no relationship between neuron number and cognitive performance (also performed in monkeys and humans) • reconstructed in 3D and counted hippocampal cells • granule cells increased in number with aged (unimpaired and impaired) rats • no statistically significant difference - basically the same • CA3/2 cells: NO statistical difference (slight decrease) • CA1 cells” NO statistical difference (slight increase) • 3. signaling dysfunction • cell numbers are NOT declining, but they are not FUNCTIONING the same way • inflammatory processes • activity at 2nd messenger receptor results in change in responsiveness of cell (neural plasticity) • neurotransmitter binds to GPCR, starts biochemical cascade • activity engages PLC • PLC cleaves PIP2 into IP3 and DAG • IP3 and DAG cause release of calcium from sequesters in ER • calcium activates PKC • PKC adds phosphates to molecules - ion channel opened via phosphorylation • NOW membrane is more responsive • eventually, phosphatase removes phosphate • can we measure activity/concentration of some of these molecules in elderly?? 2 Thursday, February 11, 2016 • place-learning in young and aged rats - aged (as a group) don’t learn as well as the young (some impaired, some not) learning index: some old do as well as the young • • measured PLC beta1 (starts process) and PP2B (phosphatase - ends process): • young have most protein • age unimpaired have no statistical difference than young (slight decline) • age impaired have a statistically significant decline in protein levels • basal forebrain nuclei some project to hippocampus • • some project to cortex - shows evidence of cellular pathology in Alzheimers • Alzheimers: • neurofibrillary tangles in cortex • TAU protein (microtubule associated protein) - accumulates and causes tangles • plaques (beta amyloid) Pittsburgh blue: labels beta amyloid (causes tangles and plaques) • • Alzheimers patients, cognitively impaired have more beta amyloid in cortex than controls • beta amyloid in membrane (function unknown) - has extracellular domains • amyloid precursor protein cleaves extracellular domains • presenilin cleaves intracellular domain NOW beta amyloid (without “legs”) is released from membrane to cause PLAQUES • • leads to loss of basal forebrain cells which product ACh (via apoptosis) —> dementia • we DON’T know why you can’t restore cholinergic function to stop dementia • epidemiological studies suggest that metfornin reduces cancer risk and mortality (usually treats diabetes - liver effects) • preserves cognitive function • activates AMP kinase and inhibits mTOR to reduce cellular energy use • in liver, reduces glucose production (which reduces serum glucose and serum insulin) • changes cellular redox status (oxidative stress) • MAY inhibit infmallation via NF kappa B, reduce insulin growthfactorlike 1, reduces oxidative damage, reduces cell proliferation in renewing tissues • effects combine to increase health span • negative age stereotypes (applied to oneself) can adversely impact health • tested by longitudinal study • also may affect you if you thought it at a young age (18-49) • more likely to have heart attack, stroke, angina, other heart issues 3


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