Shared Flashcard Set


Clinical Exam 3
Clinical Neuroscience Exam 3
Undergraduate 3

Additional Psychology Flashcards




  • rest or digest
  • ganglion closer to target organs, gives local effect
  • preganglionic in brainstem or sacral spinal cord (S1-S5)
  • preganglionic = ACh (ion cannels in AChR)
  • postganglioniuc = ACh (mAChR GPCRs)
  • preganglionic cell bodies in brainstem nuclei, including EW nucleus, salivator nuclei, and dorsal motor nucleus of the vagus and in the intermediate zone of the spinal cord
  • in pupillary light reflex, post ganglionic near the eye, preganglionic in EW nucleus
  • afferent input to ANS (NTS) = sensory ibfo from viscera (DRGS & CN9 & CN10)
  • referred pain - see later flashcard
  • fight or flight
  • ganglion far from target organs, near CNS, more post ganglion cells & a wider effect spread
  • preganglionic in thoracic & lumbar spinal cord  (C8 to L3)
  • preganglionic = ACh (ion channels in AChR)
  • postganglionic = Norepinephrine (alpha or beta GPCRs)
  • preganglionic cell bodies in inter-mediolateral column of spinal cord, lateral & medial between ventral & dorsal
  • axons emerge at dorsal root
  • some preganglionics enter splachnic nerves & synapse in autonomic plexus ganglia
  • adrenal release of  NE into bloodstream
  • sympathetic chain goes rostally & caudally
  • exception of NE is sweat glands which are cholinergic
Enteric Nervous System
  • ENS has more neurons than spinal cord
  • neurons control gut motility
  • under afferent influence of ANS, but can function on own (independently)
  • neuropeptides were first found in gut
  • visceral afferent info carried by neurons with cell bodies in DRGs & CN9 & 10 ganglia
  • information from DRGs enters spinal cord & ascends
  • info from CN9 & 10 enters brainstem & synapses in nucleus of the solitary tract in medulla (NST) - parasympathetic
  • NST info goes to hypothalamus
Cutaneous ares of referred pain
  • all go in same place (somatic & enteric)
  • over left breast & down inner left arm = cardiac (angina pectoris)
  • over sternum = esophagus
  • over right shoulder/neck muscle = diaphragm
  • between rib cage = stomach
  • under right rib cage = gallbladder
  • over belly button = small intestine
  • below belly button but above crotch = colon
  • just above crotch = urinary bladder
  • testis & kidney = up left side of crotch V
Horner's Syndrome
  • damage to cranial part of sympathetic division of visceral motor system to head and neck
  • due to damage around hypothalamus and reticular formation where it connects to visceral motor centers
  • often spare descending parasypathetic pathways that are more medial and diffuse
  • affects preganglionic targets such as neurons in interomediolateral column neuronsin spinal segmentsT1-T3 that control dilator muscle of iris & tone in smooth muscles of eyelid and globe
  • if damage is to upper thoracic outflow, the upper thoracic chain, or superior cervical ganglion, manifestiation will be limited to head and neck
  • happens if tumors down spinal cord & near it - apex of lung, thyroid, or cervical lymph nodes
  • stab or gunshot wounds
  • drooping of eyelid (ptosia)
  • ipsilateral pupillary constriction (miosis)
  • apparenty sinking of eyeball (enophthalmos)
  • also decreased sweating, increased skin temperature, and flushing of skin ipsilaterally if descending sympathetic pathway damaged
  • homeostatic control of body (body temp, shivering, sweating, circadian rhythms SCN, sleep VLPO, heart rate, blood pressure, hunger - leptin and ghrelin, thirst)
  • controls ANS, neuroendocrine
    • oxytocin, vasopressin, and more
  • visceral & emotions
  • inputs to preganglionic neurons in brainstem & spinal cord and autonomic centers in brainstem reticular formation -> visceral motor, somatic motor, neuroendocrine, and behavioral responses
  • gets input from amygdala, parabrachil nucleus, NTS, autonomic centers in brainstem reticular formation, cerebral cortex, hippocampal formation, visceral and somatic sensory pathways, chemosensory and humoral signals
  • near where BBB braks down, can determine levels of stuff in blood
  • releasing factors from hypothalamic neurons to anterior pituitary where they stimulate release of pituitary factors
  • posterior hormones: ADH, oxytocin
  • anterior hormones: ACTH, FSH & LH, GH, PRL, TSH
HPA axis
  • hypothalamus: CRH -> pituitary: ACTH -> adrenals: glucocorticoids (cortisol, lipid soluble)
  • glucocorticoids important in stress
  • glucose suppresses immune system
  • negative feedback with Rs
  • amygdala important
hypothalamus -> anterior pituitary -> targets
  • GHRH -> GH -> affect metabolism and growth and cell division
  • GnRH -> FSH, LH -> controls sex hormones (testosterone & estrogens) & gamete and sex steroid hormone production
  • TRH -> TSH -> thyroxine from thryoid = affects growth metabolism (T3T4) = thyroid hormone production
  • dopamine -> inhibits PRL (in anterior pituitary) for breastmilk production & mammary-gland growth
Hypothalamic control of eating
  • leptin made by many cell types & acts on many cells
  • after a meal, fat cells release leptin
  • leptin binds ot receptors in hypothalamus to signal satiety and inhibit hunger
  • ghrelin released by GI tract cells and binds to receptors on same hypothalamic cells as leptin, but has opposite effects
Oxytocin & Vasopressin
  • posterior pituitary
  • oxytocin  = child birth & pair bonding
  • vasopressin = ADH hormone, prevents loss of water in urine, antidieretics
  • also have effects in CNS
  • oxytocin = promote attachment & trusting
  • vasopressin = promote anxiety
Internal Carotid
  • major paired artery in brain
  • supplies the brain
ventricles & csf
  • CSF made by choroid plexus (ependyma cells with pia and subarachnoid with blood)
  • chorodid epithelium - cells specialized for secretion because basal infolding and microvilli
  • 150ml CSF (500ml made per day)
  • CSF flows through ventricles to subarachnoid space in formens (perforations in 4th ventricle) then passes through arachnoid villi on dorsal midline of forebrain & to veins via superior sagittal sinus
  • 3rd ventricl in diencephalon
  • medial surface = septum pellucidum = membranous tissue that forms part of midline to cerebral hemispheres
  • CSF from lateral ventricles flows through inter-ventricular foramen (of Munro) into 3rd ventricle to cerebral acqueduct and then to 4th ventricle
  • where parts of ventricular system become dilated due to abnormal collection of CSF
  • pressure builds up do to excess CSF, blockage, or deficient CSF reabsorption
  • obstructive = disease that restricts flow of CSF within or from ventricle - usually = blocked at ceebreal aqueduct or foramens
  • communicating = flow restrictedafter CSF has exited ventricular system so = obstructions in cisternal pathways, along subarachoid space, or at arachnoid villi


the 3 types

  • occlusive/thrombotic (50%)
    • atherosclerotic buildup in cerebral blood vessel 
  • hemorrhagic (20%)
    • cerebral blood vessel ruptures (due to hypertension or congenitial aneurysm/arteriovenous malformation, TBI, or corcaine/amphetimine)
    • most common in capsular (in internal capsule) where you get contralateral spastic hemiplegia (CS tract damage), contralateral anesthesia (damaged ascending thalamocortical fibers), contralateral lower facial paralysis (damage to corticobulbar, can get contralateral hemianopsia (damage to LGN/visual cortical fibers)
  • embolic (30%)
    • cerebral blood flow blocke dby embolus (circulating object eg atherclerotic plaque gets dislodged from heart)





  • learn brain anatomy and bloody supply "stroke by stroke"
  • use MRI and CT scans & see hemorrhagi tissue
  • doppler ultrasound, magnetic resonance angigraphy, and imaging of blood vessels by adding radiolabeled dye
  • after stroke, cell loss due to oxygen deprivation, which decreases ATP, which leads to depolarization & action poetntials releasing glutamate and get excitoxic cell death, massive calcium influx. Ischemic inury and glutamateand asp increase.
  • possibly due to prolonged glutamate activationtaht leads to lots of calcium ions acting on intracellular pathways - damage to post-synaptic cells



  • drug trials looking at NMDA antagonists and calcium channel blockers for stroke - prevent excitotixic cell death in animals, less good in patients (maybe damage happens too quickly & PCP side-effects)
  • trying magnesium to block NMDA receptors
  • drugs to reduce blood pressure (statins), anti-coagulants (aspirin, heparin, warfarin, tPA [breaks clots but then can ge hemorrhage], or endovascular devices)
  • sodium channel blockers no good
  • endothelial nitric oxide synthase (eNOS) protective, nNOs detrimental
  • hypothermia possibly good



  • plasticity of neurons as well as reduction in swelling
  • GAP43 increase near infarct and dendritic sprouding especially on contralateral side
  • paul bach-y-rita work
  • speech in left hemisphere but see activity in right after damage to left (but don't see in all)
chiari malformations
  • abnormalities in cerebellum that push on CCSF
  • when part of cerebellum is located below foramen magnum
  • may develop when ony space is smaller  than normal, causing cerebellum and brain stem to be pushed downard into the foramen magnum and into the upper sinal canal
  • resulting pressure oncerebellum and brian stem may affect functions controlled by these areas and block flow of cerebrospinal fluid
  • can becaused by structural defects in brain & spinal cord that occur during fetal develpment (genetic mutations/lack of proper vitamins or nutrients in  matenal diet) =primary/congenital CM (more common)
  • can also be caused if spinal fluid is drained excessively from lumbar or thoracic areas of spine either due to injury, exposure to harmful substances, or infection = acquired/secondary CM



  • severe pulsatile headache with other neurological symptoms
  • pain from trigeminal sometimes
  • typically affects 1/2 of head, pulsates, lasts from 2-72 hours
  • often ANS symptoms like nausea, vomiting, extreme sensitivity to light, sounds, or smells
  • can get transient aura, sensory (pins & needs, numbness, loss of proprioception), language, or motor disturbance which signals imminent headache
  • pain lasts 4-72 hours, then few days soreness, confusion
  • classic = + aura, common = no aura
  • even reversible coma, eye dysfunction, motor deficits



  • environmental (stress, hugners, foods, fatigue) and genetic predisposition (hormones too because more in females?)
  • familial hemiplegic migraine (FHM) = dominant with  mutations in voltage-gated calcium channel
  • cerebral cortex excitability and abnormal control of pain nuerons in trigeminal
  • cortical spreading depression (waves inhibitory activity) and can spread down brain to pain centers in brainstem - stimulate trigeminal nerve endings innervating the brain's vasculature and causing release of proinflammatory substances into and around the vessels resulting in vasodilationand pain



  • analgesics = aspirin, acetaminophen, NSAIDs
  • non-selective seronin agonists (ergotamine - now use more specific 5HT1B/D (inhibitory on presynaptic) receptor agonists - triptans - good for nausea and ant-emetic, maybe good vasoconstrictors (abortive treatment)
  • beta-blockers - propanolol & timolol
  • anti-epileptics - gabapentin
  • tricyclic anti-depressants - amitriptyline
  • L-type calcium channel blockers - verapamil
  • now try to block pain neurons - NK1 antagonists (Substance P antagonists) don't work, but possibly CGRP antagonists may help
  • preventive migraine medications
free radicals
  • loss of oxygenations causes formation of free radicals through genetically programmed cell death (apoptosis)
  • free radicals are very reactive and can damage DNA
  • mitochondrial DNA especiallyvulnerable becasuetehre are no good repair enzymes
  • can neutralize free radicals with enzymes (SOD and catalase)
Cortical Layers
  • 6 layers
  • layer 4 = stellate = input cells
  • layer 5 = pyramidal = output to subcotrical
  • intracortical = within a cortical area of column (input->4->2/3->5->ouput)
  • commissural = between left and right cortex (often layer 2/3)
  • association = between different areas of cortex (often layer 2/3)
  • projection (long fibers not just in cortex) = cotricofugal = leaving cortex (usually from layer 5) and corticopetal = -> cortex (usually layer 4)
areas of cortex
  • occipital = primary visual cortex = striate
    • peri & parastriate = complex visual perception so lesions lead to visual agnosia
  • parietal cortex = primary and secondary somatosensory cortices, gustatory
    • attention - attend to complex stimuli and pick out relevant ones = cognition
    • associational areas concerned with cognition of body so damage (usually to right) and get contralateral neglect syndrome
  • temporal cortex = primary auditory cortex = limbi system = emotion & memory
    • left side = verbal memory
    • right side = visually-based memory & recongition especially for things like faces
    • damage and get agnosia
    • wernicke = comprehension of language
  • frontal cortex = primary motor, pre-motor andsupplementary motor cortices
    • frontal eye field (lesions affect gaze)
    • prefrontal
      • a) DLPFC executive function - exerting cognitive control over behavior, planning, & selections tasks damage and change personality
      • b) inferior (orbital) = limbic systema nd social behavior, impulsivity
      • c) medial/cingulate = decision making & conflict
  • insula = consciousness, emotion, perception, self-awareness, cognition
  • apraxia = inability to execute learned purposeful movements, despite having the desire and the physical capacity to do so (unable to perform purposeful motor tasks like stick out tongue but can lick lips) = damage to supplementary motor areas
  • agnosias = inability to process sensory informaton, often recognition
  • neglect syndromes = patient can't recognize one side of body and things in visual field simply don't exist in their mind, can include apraxias. Sensory pathways intact. Usually damage to right parietal cortex
  • aphasia = language disorders
    • broca's = motor aphasia (sometimes with agraphia)
    • wernicke's = sensory aphasia
Lateralization in brain
  • left 
  • handwriting (central gyrus), language comprehension (wernicke's), articulation (above temporal cortex), rationalizing, calculating, intelligence (frontal)
  • right
  • drawing and art skills (central gyrus), intuition & geometric (frontal), recognition of faces (temporal), speech intonation sand gestures (parietal)
Wisconsin Card Sorting
  • frontal lobe damage and can't preform well, especially can't use previous information to guide subsequent behavior
Stroop Test
  • an attentional conflict paradigm
  • areas of cingulate cortex (ACC) and dorsolateal pre-frontal cortex (DLPFC) important for resolving conflicts
  • DLPC is last are to be myelinated in adolescents
  • striatum important for procedural memory
  • cerebellum important for motor memories
  • declarative acquisiton & consolidation in hippocampus and MTL
  • long-term memories stored in diffuse areas of cortex for delcarative info (short term in hippocampus)
  • long term memories stored in cerebellum, basal ganglia, premotor cortex, and other sites related to motor behavior for nondeclarative info
    • short term in sites unknown but presumably widespread
  • memories reconsolidated every time they are remembered
  • mamilary bodies and anterior thalamus important in memory too (Papez circuit)
  • LTP in hippocampus important in memory formation
3 Major Subdivisions of Brain
  • forebrain = telencephalon (olfactory lobes, hippocamus, cerebrum) & diencephalon (retina, pineal gland, thalamus, hypothalamus)
  • midbrain = mesencephalon = fiber tracts between anteror & posterior brain brain, optic lobes, and tectum
  • hindbrain = metencephalon (pons, cerebellum) & myencephalon (medulla)
Development of nervous system
  1. gastrulation (transcription factors and diffusible molecules)
  2. neural tube forms (transcription factors and diffusible molecules)
  3. unequal cell dvision causes bulges in the tube (transcription factors and diffusible molecules)
  4. fates of cells are specified along dorsal/ventral and rostral/caudal axes (transcription factors and diffusible molecules)
  5. neurogenesis/olgiogenesis (transcription factors and diffusible molecules)
  6. cells migrate over long or short distances (cell adesion molecules)
  7. neurons grow neurites (diffusible molecules attractants or repellents)
  8. lots of synapses form (cell surface and diffusible molecules)
  9. synapses are refined by activity and neurotrophic factors - many neurons dy  by apoptosis
  10. criticial period of time of maximum plasticity in CNS
neural tube
  1. differential rates of cell divison cause bulges to grow in certain places in the tube
  2. the position of cells within th etube determines what kin dof cell they become (cell a anterior end can becomea corticial pyramidal cell, cell at caudal end could be an alpha-motor neuron)
  3. cell fate is a result of transcription factors (Hox genes = placement of body parts) and diffusible factors (retinoic acid [RA] or BMPs)
  • divisions: prosencephalon (becomes telencephalon & diencephalon), mesencephalon, rhombencephalon
  • gastrulation: 3 layers ectoderm, mesoderm, endoderm
  • neural plate develops from ectoderm, notochord near messoderm, then neural crest inside from neural plate and in a circle as becomes neural tube and spinal cord sort of rises from that
Sonic Hedghehog (Shh, diffusible factor)
  • alar plate = dorsal = near roof plate = sensory (low [Shh])
  • basal plate = ventral = near floor plate = motor (high [Shh])
  • in between intermediate zone = interneurons & ANS pre-ganglionics
  • transcription factors also determine ventral/dorsal patterning
Neurogenesis & cell migration
  • after patterning complete, neurogenesis begins  at edge of the ventricle = ventricular zone -> up to 250,000 nuerons generated per minute
  • cells migrate from ventricle to their final position (6 layers of cortex)
  • migration controlled by manycell-surface, transmembrane molecules (cell adhesion molecules = CAMs) like delta/notch, reelin, L1CAM
  • some cells in CNS migrate long distrances = granule cells in cerebellum migrate from midbrain area, GAba-ergic interneurons in cerebral cortex migrate from the striatal area to the cortex and OB, also GnRH cells migrate from olfactory epithelium to the hypothalamus
  • top layer of cortex has to migrate through lower levels already done - layer 6 cells born first & layer 2 cells born last
neural crest derivatives
  • schwann cells
  • satellite glial cells of DRGs
  • enteric nervous system
  • connective tissue in head and neck
  • iris pigment cells
  • some dermis and adipose tissue of head and neck

Diseases of early development

environmental factors

diffusible factors

  • environmental factors
    • lack of folic acid (necessary for DNA replication) causes failure of closure of neural tube = spina bifida
    • exposure to alcohol can cause fetal alchohol syndrome (specific facial features thought to be due to defect in neural crest)
    • retinoic acid (RA) is a teratogen - seems to interfere with shh signaling
  • diffusible factors
    • mutations in shh cause holoprosencephaly (no midline - can get cyclopiatoo) & medulloblastomas (brain tumor in cerebellum)
      • basal cell carcinoma though tto be somatic mutation in SHH, PTC, and SM

Diseases of early development

transcription factors

cell adhesion & ECM molecules

  • transcription factors
    • mutation in pax6 cause aniridia (no iris ineye and mild mental retardation)
    • mutation in pax3 causes Waardenburg syndrome = craniofacial abnormalities (neural crest affected), spiana bifida and hearing loss
  • cell adhesion and ECM molecules
    • mutation in L1CAM can cause hydrocephelus
    • Fragile-X disease and fragile X protein stabilizes dendrites and synapses
    • Reelin and DCX mutations
Reeler mice
  • in reeler mutant neocortex the position of neurons is roughly reversed
  • total absence of reelin = lissencephaly  (smooth brain, large vetricles, absen cubcortical white matter)
  • reelin mutations associated with many disorders - schizophrenia, bipolar, autism, AD, TLE
  • reelin = ECM glycoprotein that affets radial migration in cortex = expressed in high levels during developing brainbut also important inadult brain and shown to lay a role in adult neurogensis, spine production, and LTP
  • classically associated with abnormally thick cortex, reduced/abnormal lamination, diffuse neuronal heterotopia (cells in wron gplace)and absence of gyri & sulci
  • doublecortin (DCX) gene (x-linked) DCX protein = microtubule-associated protein expresse din high levels during neurogenesis, also see expression of DCX increase in adult neurogenesis too
  • ARX = transcription factor
  • LIS1 gene = lis protein affects dynein (microtubule-associated rotein)
  • Reelin gene
  • mental retardation, seizures, growth faulure, high rates of spontaneous abortion
axon growth
  • cell adhesion molecules & diffusible factors with specific receptors can act as chemoattractants or chemorepulsants to help determine where axons grow
  • growth cone = diffusible & non-diffusable signals (CAM)
  • diffusable signals = attractive (netrin & anterolateral system axons crossing midline) and repulsive (robo prevents growing back again and semphorins with spinal cord and sensory neurons)
  • horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disorder characterized by congentical absence of horizontal gaze, progressive scoliosis , and failure of the corticopsinal and somatoensory axon tracts to decussate in medulla due to homozygous mutations in the axon guidance molecule ROBO3
  • anterolateral (spinothalamic) neurons carrying pain and temp info have to grow ventrally and cross the midline before they ascend to the thalamus - netrins attract these commissural axons toward the florpate so they can cross midline, then Slit turn off netrin response to prevent growth cone from crossing back again
  • semaphrins are a large family of membrane bound and diffusible factors that act on plexin receptors - they play  arole n the development of the brain as wel as of other organs - programs looking for semaphorin/plexin drugs to treat MS and spinal cord injury
  • proproprioceptive neurons (NT3 sensitive) send collaterals to LMN in ventral horn so ar e not repulsed until [semaphorin] is high
  • touch-receptive neurons (BDNF responsive) turn as they enter the spinal cord to ascend in the dorsla horns so are repulsed at intermediate concentrations of semaphorin
  • temp & pain receptive neurons (NGF responsive) are very sensitive to low [semaphorin] so they stop growing at the dorsal horn (and later form a synape with the spinothalamic neuron that crosses the midline)
synapse formation
  • initial exhuberance of nerve cells & synapses & selective death of some and reinforcement of others (DSCAM especially in flies -  38,000 alternative splicings - homophilic dingind between DSCAMs occurs and prevents synapses between axons and dendrites on sameneuron)
  • neurexins (pre-synaptic and localize synaptic vesicles and docking proteins) & neuroligins (post-synaptic - affect clustering of AMPA and NMDA receptors) much specificity of synapses but also redundancy so mutation in one protein shows little effect
  • polymorphisms have been suggested to show links to autism and schizophrenia
  • more neurons produced than can be sustained
  • more axons innervate targets than are necessary
  • target tissues produce a limited quantity of neurotrophicfactor
  • only neurons that receive enough of the neurotrophic factors survive
  • NGF (trkA) mutants lack pain & temp afferents and sympathetics
  • BDNF (trkB) mutants lack some touch afferents
  • NT3 (trkC) mutants lack some proprioceptive afferents
  • all neurotrophins important for development of PNS, target tissues provide limited supply of NTs, all activate p75 (especially pre-versions)
  • Hebb's postulate = neurons that fire together wire together
  • maximum synaptic density at 8 months
  • experience dependent plasticity & critical period = time in early development when most plasticity occurs
  • start with innate behaviors then modify circuits based on sensory input

Alzheimer's Disease


  • beta-amyloid plaques = extracellular deposits of abnormal protein = senile plaques
  • neurofibillary tangles = intracellular cytoskeletal filaments
  • spread through cortex beginning in temporal lobe
  • new predictive CSF test can predict AD
  • mutations in amyloid precursor protein (APP) (<0.1% of AD cases but virtually complete penetrance and Swedish mutation) and pre-senilin-1 & pre-senilin-2 (involved in proteolytic prcessing though tto be y-secretase components) are sufficient to cause early-onset AD
  • inheriting Apo E4 allele (involved in cholesterol processing, 3alleles at this locus), 15% frequency in Caucasians, leads to increased risk for late-onset AD (especially if homozygous)
  • rate of progression aries greatly and patients can live 4-20 years
  • preclinical phase = pathological changes occuring in cells 
  • mild cognitive impairment = neurological symptoms apparent, imaging and biomarkers cna detect alterations more reliably (CSF low AB, high tau), plaques apparent but not strongly correlated with degree of impairment
  • dementia = profound neurological symptoms, rapid decline, not associated with increase in plaque but tangles more apparent
  • gene for APP on chromosome 21 and pretty much everyone with Down's syndrome gets AD
  • B + y secretases give B42 peptide that seems to be the toxic APP molecule and makes insoluble aggregates - these could be harmful or protective

Alzheimer's Disease


  • current drugs
    • cholinesterate inhibitors (cholinergics in basal forebrain degenerate)
    • memantine is a NMDAreceptor antagonists
  • removed drugs
    • y-secretase inhibitors (cross react with notch and ntoxic to brain- GI, thymus, and spleen affected)
    • B-secretase inhibitors (cathepsin-D in pigment epithelial cells helps regenerate 11-cis-retinal and the drugs inhibit it so caused blindness in rats)
    • Antibody to AB peptide - didn'twork - Bapineuzumab - probably need to treat BEFORE plaques
    • Vaccine to AB peptipe - subacute meningoencephalitis in a subset of patients with AD after AB42 immunizations
  • Current Therapies in Trials
    • B-secretase inhibitors
    • Antibody to AB peptide - new trial in Columbia with AB antibody testing it in familial cases before onset of symptoms
    • apoptosis inhibitors
    • metal proteininteraction inhibitors
    • stem cell therapies
Prion disease
  • Kuru, Mad Cow, Scrapie, FFI, CWD -> easier to infect within a species
  • all have spongiform appearance of brain
  • prion = infectious protein and altered (beta sheet) form PrP5c catalyzes formation of more PRP5C from PRPc
  • PrP = 253 animo acid protein, GPI-linked, highly conserved, binds copper, could be copper transporter or bbe involved in synapse function
  • PrP5c is very stable, resistant to proteolysis, and also aggregates to form oligomers and higher structures
  • position 129 is either Met r Val, heterozygous individuals are more resistant than homozygotes
  • mice with mutated PrP genes can be made resistant to infection (PrP KO) or more sensitive
  • unifying theme in AD, HD, PD, Prions & ALS where specific proteins aggregate in specific neurons (proteasomes, oxidative stress, mitochondria, lysosomes, autophagy)
  • BDNF or other similar neurotrophic factors may be important in all these diseases
  • 15% of prion diseases are famila with mean age of onset 45-49 years
    • Creutzfeld-Jakob Disease
    • Gerstmann-Straussler-Scheinker syndrome
    • fatal familial Insomnia 
    • all due to mutations in PRNP
  • acquired
    • Kuru - Papua New Guinea ate brains o dead ancestors
    • vCJD - eating beef products contaimated with BSE - mean age of onset 28 years
    • latrogenic (transplanted tissue, blood transfusion, growth hormone from human pituitaries)
  • sporadic - most - no known cause
PNS repaire
  • proximal stump forms growth cone that grows along old path - stimulated by diffusible factors (BDNF) and extracellular matrix molecules secreted by Schwann cells and target organs
  • crush injury more rapid recovery than a cut
  • macrophages rapidly remove myelin debris and proliferating schwann cells promote axon regeneration
  • AChr & AChe remainds after damage nadneruons grow back and and make NMJ synapses in same place as before injury
  • slow regeneration
CNS repair
  • neurogenesis happens in fish retina & songbirds
  • in mammals, neural stem cells in ventricle walls and migratevia RMS to olfactory bulb
  • ORNs develop in OE throughout life and make synaptic connetions in the OB
  • also neural stem cells in dentate gyrus of hippocampus
  • BDNF signaling required in adult CNS for maintenance of neurons and circuitry
  • BDNF mutants have impaired spatial learning in Morris Water Maze, have generalized fear and increased depression, also aggressive
  • BDNF importantto maintain spine density of neurons
  • anti depressants cause BDNF to increaase and dendritic arborization to increase - neurogenesis in hippocampu safter antidepressants
  • BDNF expressedvin many neurons including VTA and in pyramidal neurons in mPFC which is anterogradely ransported to NAc, region with minimal BDNF expression
Spontaneous vs Forced
  • if have lesion of UMN from motor cortex hardto move muscles in lower face on contralateral side - so have a hard time showing teeth voluntarily but have an involuntary smile response (Duchenne smile)
  • if have tumor in thalamus that affects descending pathways fromnon-classical motor areas (ACC), then get emotional facial paresis (Pyraidal smile)
  • volitional movement of descending "pyramidal" and "extrapyramidal" projections from motor  cortex and brainstem input on motor neuron pools in facial neurons
  • neural systems for emotional experssion of descending "extrapyramidal" projects from medial forebrain adn hypothalamus input to motor neuron pools in facial nucleus
Limbic areas involved in emotion  & mood
  • cingulate (mood, too) & limbic cortex
  • amygdala  (mood, too)
  • ventral and basal ganglia = nucleus accumbens  (mood, too)
  • hypothalamus  (mood, too)
  • emotions include visceral responses via hypothalamus & RF (if both severed, no sham rage)
  • orbital and medial prefrontal cortex (mood)
  • hippocampus (mood)
  • ACC (monitor failure) (mood)
  • areas for pain, conflict
  • also reward pathways
Fear Circuits
  • overall effect = arousal, vigilance, enhanced memories
  • input to amygdala from sensory thalamus & sensory cortex to amygdala
  • output to hypothalamus (sympathetics & HPA axis), PAG (descending analgesic pathways & freezing), LC (NE increase), Raphe (serotonin increase), and VTA (DA increase)
  • cued fear (associated with a footshock) involves amygdala
  • contextual fear (where they get the footshock) involves hippocampus
  • emotional component = amygdala (damage = consciously recall stiumulus but not autonomic response)
  • cognitive component = hippocampus (damage = have autonomic response & can consciously recall)
  • emotional enhancement of fear-associated memories involves NA acting on B-adrenergic receptors in the amygdala & this signals the hippocampus
  • beta blockers (propranolol) can be used to remove some of the emotional components of stressful memories
  • state of preparation for danger but in absence of immediate danger signal
  • anxiety disorders involve abnormal regulation of amygdala-based fear circuitry, often involves extended amygdala & generalized activations of pathways (amygdala hyperactive with trauma recall or fearful faces)
  • types of anxiety:
    • panic disorder
    • generalized anxiety disorder (GAD)
    • PTSD
    • simple phobias
    • social phobia (social anxiety disorder)
    • obsessive-compulsive disorder (OCD) - maybe more related to Tourette's syndrome and striatal circuits are disrupted
  • treatments
  • cognitvie behavioraal therapies, eye movement desensitization and reprocessing (EMDR)
  • benzodiazepines (low potency for GAD, high potency for panic) - fast onset but sedative side-effects - GABA
  • barbiturates (side effects) - GABA
  • alcohol (self-administered) - GABA
  • beta blockers
Recreational & Addictive Drugs
  • psychostimulants
    • amphetamine= release of DA, NE, 5HT (high doses), also DA and NE reuptake inhibition used for ADHD (Ritalin), chronic fatigue syndrome, narcolepsy
    • cocaine = specific for DA transporter
    • methamphetamine = release of DA, NE, 5HT (More than amphetamine), also DA & NE reuptake inhibition
  • opiates = morphine & heroin = reinforcing effects and unplasant withdrawal effects, compulsve abuse, disinhibition of VTA DA neurons, some effects in NAc independentof DA - will work for opiates even with a DA antagonist
  • ethanol = CNS depressant serious health problems because need lots for effect - activates GABAA, NMDA antagonist but no psychotic effects like PCP and ketamine, acts in reward (VTA or NAc), acts via opiates so block reinforcing effects with naltrexone
  • MDMA = Ecstasy, 5HT2A release & reuptake inhibition, lesser effects on DA & NE
  • LCD = hallucinogens, like Ecstasy
  • nicotine = carcinogenic because other compounds in cigarettes = nACHr agonist act on DA possibly in VTA
  • THC = don't see withdrawal because it says in body for along tiem but can recipitate with a THC antagonist
  • PCP & ketamine = NMDA antagonist, reinforcing dissociative anesthetics
Striatal Limbic Loop
  • important in addiction and depression 
  • emotional reinforcment of addiction due to limbic feedback loop in ventral basal ganglia
  • limbic loop = cortex (amygdala, hippocampus, temporal lobe, orbitofrontal lobe, anterior cingulate cortex) -> ventral striatum (NAc) -> ventral pallidum (+SNPR) -> MD thalamus

Mood Disorders

major depression symptoms

  • often people with mood disorders have anxiety
  • bipolar disorder (manic depressive illness)
  • dysthymia (mild but long term depression)
  • Major Depression
    • ACC overactive in depression
    • HPA axis often over activated in depression (cortisol increased possibly due to hypothalamus or amygdala increase or hippocampus decrease)
    • hypothalamus probably involved in behavioral symptoms in depression such as sleep and appetite changes
    • amygdala activated hypothalamus & CRF release, hippocampus inhibits hypothalamic output of CRF
    • hippocampal atrophy in depression (maybe lots of GC receptors in hippocampus - GC act via BDNF?
    • reward pathways affected through most current anti-depressants treat 5HT and/or NA synapses
    • stress may cause excitotoxicity in hippocampu sand cause reduction in BDNF (GC act via BDNF)

Depression Treatments

Bipolar Treatments

  • depression
    • MAOI = MAOI-A in liver and side effects (tyramine in cheeses)
    • tricyclics = act on NA and 5HT
    • SSRIs, NRIs, SNRIs,
    • Ketamine
    • cognitive behavioral therapy
    • ECT (&TMS, deep brain, vagal stimulation)
    • anti-depressants take weeks to have clinical effect, maybe due to adaptation of monamine pathways to increased availability of 5HT or NE, possible neurogenesis = see neurogeneis increase & BDNF increase in hippocampus
    • NEW: CRF antagonists, kappa opioid antagonists, CB1 agonists or antagonists, cytokines, melatonin agonists, galanin (in NE and 5HT neurons), NPY agonists, histone deacetylase inhibitors - promote synaptic plasticity, TPA (may mediate stress effects?)
  • Bipolar
    • lithium
    • anti-convulsants (valproic acid -> GABA)
  • complex degenerative disorder
  • positive = psycotic ones and include disordered thoughts, delusions, and hallucinations (auditory), psychosis (loss of contact with reality - paranoia, delusions, disconnected thought)
  • psychotropic drugs alter behavior, mood, perception (mood disorders may have psychotic events too)
  • negative = absence of emotion or emotional flatness, loss of motivation, social interaction, blunting of affect
  • cognitive = deficits in executive function (working and episodic memory), defects in stroop test, language deficits
  • genetic component but environment important
  • neuregulin mutated, neurexins important for synapse formaton, proteins important in G-protein signaling
  • accelerated loss of gray matter in adolescence
  • enlarged lateral ventricles and decreased spines in DLPFC
  • altered neurotrophins
  • treatment:
    • anti-psychotic drugs = D2 antagonists (treat positive, not good fo rnegative or congiitve defects, Parkinson-like side effects)
    • new anti-psychotics = weaker D2 antagonists & more activity on other receptors, like anti-depressants and exert clinical effects over weeks
    • nAChR agonists (schizophrenics smoke a lot), NMDA co-agonists (D-serine, PCP is an NMDA antagonist and causes hallucinations)
    • SSRIs often effective
  • cognitive disorder but similar circuits and drugs as for mood disorders
  • deficits in executive function, workin gmemory, reduced ability to maintain cognitive control of behavior
  • inattention, impulsive, hyperactive (ADHD)
  • strital loops (DLPFC -> striatum -> globus pallidus -> thalamus) in ADHD
  • DA from VTA affects these loops (like in Parkinson's)
  • DA from VTA and NE from LC affect PFC cells directly
  • treatment
    • amphetamines & methylphenidate = psychostimulants that increase DA in synaptic cleft by preventing reuptake of DA into presynaptic terminal (slow release preparations of amphetamine cause less addiction)
    • NRIs - inhibit reuptake of NE
    • a-adrenergic agonists


description & diagnosis

  • seizures = uncontrolled synchronous rhythmic firing of neurons in brain
  • epilepsy = recurrent & unpredictable seizures, can cause excitotoxicity and spread of foci (focus - area where seizure began), 1/20 peopl ehave seizure and epilepsy is 1/200 people
  • diagnosed by EEG (large spikes, synchronous rhythmic activity during seizure and location correlates with behavioral effects) but doesn't always work - 5% without epilepsy have abnormal EEG and 20% of people with epilepsy have normal EEG
  • MRI or CT can find location of a scar or damaged brain tissue
  • PET examine brain blood flow 


types - generalized

  • generalized = uncontrollable discharge of neurons on BOTH sides of brain, most common type, starts in one area and spread across, produce muscle twitches & convulsions & loss of consciousness so no memory of seizure
  • tonic-clonic (grand mal) = massive discharge of neurons on both cerebral hemispheres, immediate loss of consciousness, ordered sequence of muscle events, body becomes rigid (tonic = extension of extremities) and then clonic (jerkiness, twitching of body - often unmanageable by drugs), common in children
  • absence (petit mal) = nonconvulsive, brief loss of consciousness, only lasts 5-30 seconds, reticular thalamus shows rhythmic burst firing when reduced consciousness but when awake & alert, tonic single spikes (3Hz), treated with Ca2+ channel blockers (ethosuximide) - GABA agonists can make this seizure worse
  • myocloinc = twitching or jerking of single twtich event = motor cortex firing
  • atonic seizure = loss of muscle tone and causes a person to fall down = no loss of consciousness
  • status epilepticus = frequent long-lasting seizures without regaining consciousness between attacks, requires immediate medical attnetion


types - partial

  • partial = abnormal electrical activity involving only a small part of the brian but often can spread & become generalized
  • simple partial = focal seizures, short-lasting without lsos of consciousness, if in SS cortex see & hear or smell something strange or get pins & needles, hot/cold in area of body, adversive and head/eyes move to contralateral side (in PFC/primary motor), focal motor = clonic twitching of contralateral muscles (can become tonic/clonic grand mal)
  • complex partial/psychomotor = impairment of consciousness, affects complex processes like speech, emotion, or memory, can have hallucinations or deja-vu, aphasic and can't speak, write, or read, usually initiate in higher asociation cortices and often include temporal lobe, TLE = damaged hippocampus and reorganized dentate granule cells
Epilepsy causes
  • 50-70% have no known cause
  • many get seizures but 10% get epilepsy
  • genetics (channelopathies)
    • Ca2+ channel mutations can cause familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2)
    • Na+ channel mutations can cause generalized epilepsy with febrile seizures (GEFS)
    • k+ channel mutations cause benign familial neonatal convulsions (BFNC) and episodic ataxia type 1 (EA1)
    • mutations in Na+ channels slow inactivation of Na+ currents in GEFS
  • head injuries
  • brain tumor (cancer therapies too?)
  • stroke/arteriosclerosis
  • pre-natal (injury/infection/lack of oxygen)
  • infection (meningitis or encephalitis)
  • can cause brain "scar" that can lead to epilepsy
  • kindling model in rodens = series of sub-threshold electrical stimulations eventually DO cause a seizure and then get spontaneous seizures without electrical stimulation
  • individual seizures caused by stress, lack of sleep, flashing lights or sounds, low blood sugar, fever, alcohol/benzodiazepine withdrawal, hormones (estrogenand seizures possibly act via BDNF)



  • enhance GABA action (barbituates & benzodiazepines but if drug stop it can lead to more seizures)
  • Na+ channel blockers (phenytoin)
  • Ca2+ channel blockers (ethosuximide - for absence seizures, acts in reticular thalamus to inhibit 3Hz spikes)
  • Valproate (blocks Na & Ca2+ channels, increases GABA levels, inhibits histone deacetylases so may counteract aberrant neurogenesis)
  • Topiramate (effets on Na&Ca2+ channels, GABAA receptors, and ionotropic glutamate receptors)
  • SSRis (plasticity?)
  • surgery when resistant to drugs
  • temporal lobe - part of temporal lobe, hippocampus & amygdala
  • corpus callosotomy (split brain) - prevent spreading
  • hemispherectomy - not done often, children can function quite well though they often have trouble using arm on contralateral side, sometimes only specific lobes removed
  • ketogenic diet = high fat, low protein/carbohydrate (like Atkins)
  • biofeedback = people trained to control EEG patterns to shorten seizures
  • counterstimulation (romans applied electric eel? now use invasive electrodes)
  • exercise
  • relaxation techniques
  • vagus nerve stimulation (electrical stimulator implnated to stimulate vagus nerve)
  • vitamin & mineral supplements
Stress & HPA axis
  • brain regions involved with Stress: hypothalamus, amygdala (+ on hypothalamus), hippocampus (- on hypothalamus)
  • dorsal raphe affects amygdala & hippocampus
  • when stressed, hippocampus inhibited (elevated glucocorticoids and severe traumatic stess and excitatory amino acid NTs cause atrophy) and only have positive on hypothalamus & increase stress response
  • hippocampus show greater changes than other brain areas especially in Cushing's, depressive illness, PTSD, schizophrenia, and aging prior to overt dementia
  • HPA dysfunctions thought to be involved in chronic fatigue syndrome, cushing's syndrome, anxiety, major depression, schizophrenia, irritable bowel syndrome
Panic Disorder & HPA axis
  • dysfunctional serotonergic system arising frm dorsal raphe thought to be involved in etiology and pathophysiology of panic disorder
  • subpoplation of 5HT neurons control sympathetic & motor responses to aversive stimuli
  • 5HT neurons in DRVL/VLPAG reduce panic, inhibit activation of DPAG that gives fight or flight response
Supporting users have an ad free experience!