Flashcards in Lange 7 Deck (159):
what does the resting membrane potential close to?
Ek because K+ is the major determinant of the charge difference across a membrane
when are neurotransmitters released?
Ca++ dependent exocytosis
inhibitory neurotransmitters and actions
GABA and glycine: open Cl- channels causing inhibitory postsynaptic potential
what happens when NE binds B-adrenergic receptors?
activates adenylyl cyclase and stimulates the production of cAMP which activates the cAMP-dependent protein kinase that can phosphorylate voltage-gated calcium channels
what are the alpha1-adrenergic, muscarinic cholinergic, and metabotropic glutamate receptors coupled to?
phospholipase C which catalyzes the hydrolysis of the membrane lipid phosphatidylinositol-4,5 bisphosphate causing two second messengers: 1,2 diacylglycerol (activates enzymes in protein kinase C family) and inositol-1,4,5 triphosphate (binds intracellular receptor that is a calcium ionophore allowing release of calcium from intracellular stores into cytosol)
-regulate K and Ca concentrations within the interstitial space
-provide structural and trophic support for neurons through production of extracellular matrix molecules such as laminin and release of growth factors
-provide sites for release of cytokines and chemoattractants at blood vessels during CNS injury
-respond to brain injury by increasing and size and sometimes number
-important role in terminating neuronal responses to glutamate
-contain glutamine synthase (converts glutamate to glutamine) - detoxifies CNS of glutamate and ammonia
reside in CNS functioning as main immune effector cells - activated by brain injury, infection, or neuronal degeneration
damage to the lower motor neurons results in what?
loss of all voluntary and reflex movement (flaccid weakness) and muscle tone or resistance to passive movement is reduced
describe the path of motor neurons from brain to muscle
begin in principal motor area (precentral gyrus) which can also receive input from premotor area -> converge in corona radiata -> posterior limb of internal capsule -> cerebral peduncles -> central pons -> ventral medulla -> cross in pyramidal tract where most dessucate -> lateral corticospinal tract
what are the extrapyramidal neurons?
neurons in the caudate nucleus, putamen, globus pallidus, red nuclei, subthalamic nuclei, substantia nigra, reticular nuclei, neurons of the cerebellum. they are connected to the motor corticospinal and corticobulbar tracts but distinct from these cortical motor (pyramidal) neurons
what is the purpose of extrapyramidal neurons?
important for complex patterns of movement and for coordinating motor responses to sensory stimuli
each alpha motor neuron axon contacts up to 200 muscle fibers
what do tendon reflexes and muscle tone depend on?
activity of alpha motor neurons, specialized sensory receptors known as muscle spindles and small gamma motor neurons whose axons innervate the spindles
antibodies to calcium channels inhibit calcium entry into nerve terminal and reduce neurotransmitter release - repetitive nerve stimulation facilitates accumulation of calcium and increases Ach release
what causes a similar syndrome to lambert-eaton syndrome?
cleaves specific presynaptic proteins preventing neurotransmitter release at both neuromuscular and parasympathetic cholinergic synapses
when do fibrillations occur?
in denervated muscles - receptors are not clustered and are spread across the muscle membrane
what are the upper motor neurons?
cortical motor neurons that converge in the corona radiata then descend in the posterior limb of internal capsule, cerebral peduncles, ventral pons, and medulla
neurons that innervate lower facial muscles are what?
primarily crossed fibers
motor neurons for the legs are found where?
medial surface of the hemisphere (face on ventral end of the central sulcus)
unilateral upper motor neuron lesions are characteristic how?
muscles innervated by lower motor neurons that receive bilateral cortical input such as eyes, jaw, upper face, pharynx, larynx, neck, thorax, abdomen are spared
upper motor neuron lesions appear how?
characteristic pattern of limb weakness and change in tone - antigravity muscles become more active, arms flex, pronated posture, legs become extended while muscles that move limbs out of this posture (extensors or arms and flexors of legs) are weakened
-tone is increased in antigravity muscles "clasp knife phenomenon"
what is clonus? when is it present?
series of involuntary muscle contractions in response to passive stretch - upper motor neuron lesions especially with spinal cord
how to tell if a lesion is above or below the pons
above the pons: impair movements of contralateral lower face, arm and leg
below the pons: spare the face
lesions of the internal capsule vs cortex
internal capsule: impaired movements of contralateral face, arm, leg equally
cortex: differentially affect the limbs and face because motor fibers are spread over larger area of brain
what are the three regions of the cerebellum?
flocculonodular lobe (flocculus and nodulus of vermis)
anterior lobs (remainder of vermis)
cerebellum - controls posture and eye movement
receives proprioceptive input from muscles and tendons via the dorsal and ventral spinocerebellar tracts and influences posture, muscle tone, and gait
important for coordination and planning of voluntary skilled movements initiated from cerebral cortex
superior cerebellar peduncles
efferents from cerebellar cortex to red nucleus and thalamus
simple movements are delayed in onset and rates of acceleration and deceleration are decreased (intention tremor and dysmetria (overshooting)) due to cerebellar disease
lesions to cerebellar hemispheres vs midline lesions
hemispheres: affect the limb (limb ataxia)
midline lesions: axial muscles (truncal and gait ataxia + disorders of eye movement)
cerebellar lesions are associated with.....
hypotonia as a result of depression of activity of alpha and gamma motor neurons
what areas of the brain regulate voluntary movement and maintaining posture
basal ganglia, globus pallidus, substantia nigra, subthalamic nuclei
what is the main function of the basal ganglia?
regulate the initiation, amplitude, and speed of movements
where is dopamine synthesized?
parkinson's disease pathology
degeneration of nigral neurons leads to loss of dopaminergic inhibition and a relative excess of cholinergic activity - this increases GABAergic output from the striatum and contributes to the paucity of movement that is a cardinal manifestation of the disease
AD - involuntary, rapid, jerk movements (chorea) and slow writhing movements of the proximal limbs and trunk (athetosis)
what gene is implicated in huntington's disease? which chromosome is it found on?
huntingtin trinucleotide (CAG) repeat on chromosome 4 - involved in intracellular trafficking and endocytosis, gene transcription, and intracellular signaling - GAIN OF FUNCTION
what promotes the striatal cell loss in huntington disease?
loss of neurotrophic support and enhanved caspase activity
confers information about touch, pressure, temperature, pain, vibration and position and movement of body parts -> relayed to thalamic nuclei and integrated in the sensory cortex of the parietal lobes to provide conscious awareness of sensation
describe the path of sensory nerve fibers
dorsal roots enter the dorsal horn - large myelinated fibers divide into ascending and descending branches and synapse in dorsal column or travel in dorsal columns -> terminate in the gracile or cuneate nuclei of lower medulla on SAME SIDE -> cross the midline in the medulla and ascend to the thalamus as the medial lemniscus
where are new fibers added in the dorsal columns?
leg fibers medially, arm fibers laterally
dorsal column-lemniscal system carries what?
information about pressure, limb position, vibration, direction of movement, recognition of texture and shape, and two point discrimination
lateral spinothalamic tracts
pain, temperature, and touch sensation - ascend in anterolateral spinal cord - cross IMMEDIATELY in anterior white commissure
where do fibers carrying information about pain and temp sensation terminate?
nucleus of the spinal tract of cranial nerve V
which fibers convey sensory info in response to chemical, thermal, and mechanical stimuli - what evokes pain?
free nerve endings of unmyelinated C fibers and small diameter myelinated Alpha Delta fibers in the skin - intense stimulation = pain
how is pain in deep tissues evoked?
inflammatory conditions sensitize by bradykinin, prostaglandins, leukotriences released
abnormal painful sensations - also called neuropathic pain that has a strange buring, tingling, or electric shocklike quality due to damage of pain pathways
how is proprioception and vibratory sense relayed?
receptors in muscles, tendons, joints relayed to spinal cord via large Aalpha and Abeta myelinated fibers and to the thalamus by the dorsal column-lemniscal system
what is often impaired with proprioception?
what are the primary modalities of sensation?
touch, pain, temp, vibration
damage to sensory cortex or its projections from thalamus has preservation of what?
primary modalities of sensation
loss of pain and temperature sensation on one side of the body and of proprioception on the opposite side occurs with lesions that involve one half of the cord on the side of the proprioceptive deficit
what happens in syringomyelia
enlargement of the central cervical canal causes loss of pain and temp sensation across the shoulders and upper arms (cape like)
what fibers do the optic tracts contain?
fibers from the same half of the visual FIELD of both eyes
where do the optic tracts terminate?
lateral geniculate nuclei of the thalamus
III: innervates the ipsilateral medial, superior, and inferior rectus muscles and the inferior oblique muscles
also supplies the ipsilateral levator palpebrae which elevates teh eyelid
carries parasympathetic fibers taht mediate pupillary constriction
IV: supplies CONTRALATERAL superior oblique muscle
VI: lateral rectus muscle of the same side
vertical gaze center
lateral gaze centers
pontine paramedian reticular formation
sends fibers to the neighboring ipsilateral abducens nucleus and via the medial longitudinal fasciculus, to teh contralateral ocularmotor nueluc (causing activation fo teh right lateral gaze center stimulating conjugate deviation of the eyes to the righ
what are slower eye movements involved in?
parieto-occipital gaze centers - stimulate conjugate gaze to teh side of the gaze center
nuclei of edinger-westphal
parasympathetic oculomotor nuclei - sends fibers in teh oculomotor nerves that synapse in the ciliary ganiglia within the orbits and innervate the pupillary constrictor muscles
what is the three-neuron system for the motor portion of pupillary dilation?
axons from neurons in posterolateral hypothalamus -> lateral brainstem tegmentum -> cervical spinal cord to teh level of T1 ->terminate on preganglionic sympathetic neurons within the lateral gray matter of the thoracic cord -> neurons send axons that synapse with postganglionic neurons in the superior cervical ganglion ->fibers that travel with the internal carotid artery and the first divions of trigem to innervate the iris
where are cones
macular region - bright light and discrimination of color
what is an early sign of disorders of retina or optic nerve?
diminished color discrimination
where are geniculate fibers in the occipital lobe?
layer IV of the visual cortex
lesion of optic chiasm
disrupt crossing fibers from the NASAL halves of both retinas: bitemporal hemianopia
lesions involving structures behind the chiasm: completely destroy optic tract, lateral geniculate nucleus, or optic radiations on one side
cause visual loss in the contralateral field of both eyes: homonymous hemianopia
slective destruction of temporal lobe optic radiations
parietal optic radiation lesions
where do fibers from each retina terminate?
pupillary constrictor fibers release what?
acetylcholine, activating muscarinic AChRs which stimulates contraction of the pupillary sphincter muscle of the iris
sympathetic pupillary fibers release what, activating what, causing contraction of what?
NE, alpha 1 adrenergic receptors, contraction of radial muscle of the iris
what drug inhibits muscarinic receptors? what drug stimulates alpha 1-adrenergic receptors? what does this cause?
dilate the pupils
vestibular nuclei exert control over what?
middle ear function
amplify and transmit sounds to the cochlea - specialized sensory cells are organized to detect ranges in amplitude and frequency of sound
diseases of the external or middle ear taht impair conduction and amplification of sound from the air to the cochlea
diseases of the cochlea or eighth cranial nerve
diseases affecting the cochlear nuclei or auditory pathways of the CNS (uncommon because of redundancy of central pathways)
when is rinne test positive?
when the sound is louder at the meatus - sensorineural deafness - middle-ear structures are intact (conductive deafness, sounds are heard less well through air and the test is negative)
weber test positive
placed at midline: conductive deafness, sound is heard best in the abnormal ear, whereas sensorineural deafness the sound is heard best in the normal ear
difference between vestibular and cerebellar disequilibrium
cerebellar is more coordination rather than a feeling of dizziness in the head
what are the two types of vertigo and which is worse?
peripheral vertigo (worse because nausea and vomiting due to disease of labyrinth or vestibular nerve) and central vertigo (dysfunction of brainstem and CNS pathway)
what are causes of central vertigo?
brainstem ischemia, brainstem tumors, multiple sclerosis
how does uncal herniation cause coma?
expanding mass in temporal lobe compresses first the third cranial nerve causing pupillary dilation and impaired function of eye muscles - continued pressure distorts the midbrain putting the patient in coma with posturing of the limbs
how do you tell the difference between metabolic vs structural comas?
metabolic will have pupillary light responses preserved despite impaired oculovestibular or respiratory function
which neurons are important for sleep?
neurons in the dorsal midbrain and especially nuclei within the pontine reticular formation
lesions in the pons preserve what but disturb what?
preserve consciousness but disturb sleep
prefrontal cortex is important for what?
orderly planning and sequencing of complex behaviors
frontal lobe syndrome is due to what?
damage to the frontal lobes or connections to the caudate and dorsal medial nuclei of the thalamus causing dramatic alterations in personality and behavior
unilateral damage to prefrontal cortex causes what?
subtle alterations in behavior that may be difficult to detect.
premotor area involvement can lead to incontinence, inability to perform learned motor tasks (apraxia), varialbe increases in muscle tone (paratoni) and appearance of primitive grasp and oral reflexes
lesions in frontal speech causes what?
nonfluent, dysarthric, halting speech
lesions in temporal speech area causes what?
fluent speech that contains many errors or may be totally devoid of understandable words
damage to the inferior parietal region causes what?
agraphia (inability to write) because this area is important for the translation of linguistic messages generated in the temporal language areas into visual symbols
alexia is due to what?
isolation of the temporal speech area from the occipital lobes (inability to read)
limbic system: where is it and what does it do? damage to it causes what?
hippocampi and their connections to the dorsal medial nuclei of the thalamus and the mammillary nuclei of the hypothalamus.
crucial for learning and processing of events for long-term storage
damage causes inability to learn new material or retrieve memories from recent past
motor neuron disease affect what and are characterized by what?
predominantly affect teh anterior horn cells of the spinal cord and characterized by wasting and weakness of skeletal muscles - spontaneous discharges of degenerating motor nerve fibers occur, giving rise to muscle twitches (fasciculations)
spinal muscular atrophies are characterized by what?
selective degneration of lower motor neurons
SMAI - infantile spinal muscular atrophy - die within 3 years seen by 3 months - difficulty sucking, swallowing, breathing - atrophy and fasciculation are found in tongue and limb muscles
latter half of the first year of life - progresses more slowly than infantile form and patients may survive into adulthood
SMA III - develops after age 2 - weakness of proximal limb muscles with relative sparing of bulbar muscles - gradually progressive - disability in adulthood
SMA are all due to what?
deletions or mutations in the survival motor neuron 1 (SMN1) on chromosome 5 - loss promotes apoptosis of LMN
amyotrophic lateral sclerosis
mixed upper and lower motor neuron deficits found in limb and bulbar muscles - initial symptoms weakness of limb muscles - bilateral but asymmetric
either open cation channels (ionotropic receptors) or activate phospholipase C (metabotropic receptors) which catalyzes second messanger IP3 which stimulates release oc Ca2+ from intracellular stroage sites
how is glutamate removed in synapses?
by transport proteins on surrounding astrocytes where it is metabolized to glutamine (then shuttled back to neurons) - or is just taken up by neuron
glutamate and ALS
there is a large decrease in glutamate transport activity in the motor cortex and spinal cord but not in other regions of CNS
what gene contributes to ALS pathogenesis?
GluR2 (glutamate receptor)
SOD1 (cytosolic copper-zinc superoxide dismutase) - gain of function causing free radicals
cytoskeletal proteins in ALS
neurofilament dysfunction in ALS supported by neurofilamentous inclusions in cell bodies and proximal axons
transactive-response DNA-binding protein 43 - major component of the ubiquitinated, tau-negative, inclusions that are pathological hallmark of sporadic and familial ALS and frontotemporal dementia (located on chromosome 1)
clinical syndrome of rigidity, bradykinesia, tremor, postural instability
selective degeneration of mono-amine-containing cell populations in the brainstem and basal ganglia, particularly of pigmented dopaminergic neurons of substantia nigra
exposure to which toxin can cause parkinsonism?
MPTP, manganese, carbon disulfide, carbon monoxide
what drugs can cause reversible parkinsonism?
butyrophenones, phenothiazines, metoclopramide, reserpine, tetrabenazine
wilson disease can cause what?
characteristics of parkinson disease
lewy bodies (eosinophilic, cytoplasmic inclusion bodies) containing filamentous aggregates of alpha-synuclein
how does MPTP cause parkinson disease?
enters brain -> converted by monoamine oxidase B present in glia and serotonergic nerve terminals to MPDP+ which diffuses across glial membranes -> nonenzymatic oxidation and reduction to MPP+ (active) which inhibits oxidative phosphorylation by interacting with complex I -> no ATP -> increased free radicals that cause cell injury
what part of the cell appears to play an important role in pathogenesis of parkinson disease?
complex I (due to MPTP mechanism)
gene for alpha-synuclein that causes parkinson's
PARK1 on chromosome 4 - AD - formation of lewy bodies -> reduced dopaminergic terminals in striatum, impaired motor performance due to formation of abnormal complexes at the synapse with SNARE proteins
major structural abnormality in myasthenia gravis
simplification of the postsynaptic region of the neuromuscular synapse - muscle end plate shows sparse, shallow, and abnormally wide or absent synaptic clefts - 70-90% decrease in number of receptors (increased receptor internalization and degradation due to antibodies)
cholinergic crisis in myasthenia gravis
therapy with cholinesterase inhibitors can cause paradoxical increase in weakness due to continued exposure of agonist causing desensitization
what do patients without IgG in myasthenia gravis have? what treatment is effective?
they have MuSK antibody - patients are younger women with muscle atrophy - plasma exchange is effective
generalized tonic-clonic seizures
attacks characterized by sudden loss of consciousness followed rapidly by tonic contraction of muscles causing limb extension and arching of back (10-30 seconds) followed by clonic phase of limb jerking
brief lapses in consciousness lasting several seconds without loss of posture - eyelid blinking, slight head movement, brief jerks of limb muscles
what is apparent on EEG of absence seizure?
spikes and waves at a rate of 3 per second (particularly after hyperventilation)
simple focal seizures
begin with motor, sensory, visual, psychic, or autonomic phenomena depending on location of the seizure focus - consciousness is preserved unless seizure discharge spreads to other areas causing secondary generalization
focal dyscognitive seizures
characterized by the sudden onset of impaired consciousness with stereotyped, coordinated, involuntary movements (automatisms)
where is the seizure focus typically?
temporal or frontal lobe
what are seizures characterized by on EEG?
neurons are activated synchronously
NMDA receptors and seizures
normally - NMDA channels preferentially pass calcium ions but are relatively quiescent during normal synaptic transmission because they are blocked by magnesium ions - magnesium block is relieved by depolarization
secondary epilepsy mechanism
loss of inhibitory circuits and sprouting of fibers from excitatory neurons appear to be important for the generation of a seizure focus (may have mutations in ion channels)
what are absence seizures due to?
synchronous thalamic discharges that are mediated by acitvation of low-threshold calcium currents (T or "transient" currents)
what drug is used to block T channels and suppress absence seizures in humans?
anticonvulsant ethosuximide (blocks T channel)
when are T channels are more likely to be activated when?
after hyperpolarization of the cell membrane
abnormal regulation of what receptor may be important in the pathogenesis of absence seizures?
impairment of memory and at least one other area of cortical function - language, calculation, spatial orientation, decision making, judgment, and abstract reasoning - symptoms progress, incidence increases with age
what are the treatable causes of dementia?
hypothyroidism, vitamin B12 deficiency, neurosyphilis, brain tumor, normal pressure (communicating) hydrocephalus, chronic subdural hematoma
what is the pathology of alzheimer's characterized by?
extra cellular neuritic plaques in the cerebral cortex and in walls of meningeal and cerebral blood vessels - plaques have dense core of amyloid material surrounded by dystrophic neurites, reative astrocytes, and microglia
also have intraneuronal neurofibrillary tangles (hyperphosphorylated microtubule protein tau)
treatment for alzheimer's
cholinesterase treatments such as donepezil, rivastigmine, galantamine
where are pathologic changes most prominent in alzheimer's
hippocampus, entorhinal cortex, association cortex, and basal forebrain
AB amyloid in AD
toxic to cultured neurons and stimulates production of cytokines from microglial cells - also triggers release of glutamate from glial cells injuring neurons through excitotoxicity
presenilins in AD
gamma secretase cleaves fragment to yield AB - increase in production of AB42
apolipoprotein E in AD
majority of patients have e4 isoform of apoE4 - mediates teh binding of lipoproteins to the LDL receptor
apolipoprotein e2 vs e3 vs e4
e3 normal: binds tau much more avidly than e4
e4: increased risk for alzheimers
e2: decreased risk
vascular occlusion interrupts blood flow to a specific brain region, producing a fairly characteristic pattern of neurologic deficits resulting from loss of functions controlled by that region
less predictable pattern because it depends on the location of bleed
ischemic strokes involving small arteries result from?
degenerative change in the vessel described as lipohyalinosis - caused by hypertension and predisposes to occlusion (most common lenticulostriate which perfuse the basal ganglia and internal capsule)
lacunar infarctions typically occur where?
putamen, caudate, thalamus, pons, internal capsule
epidural hematomas arise from what?
damage to artery - typically middle meningeal due to blow to temporal bone
subdural hematomas arise from what?
venous blood that leaks from torn cortical veins bridging the subdural space - minor trauma - low pressure - no symptoms for several days
subarachnoid hemorrhage occurs from what?
head trauma, extension of blood from another compartment into the subarachnoid space, or rupture of an arterial aneurysm
what does cerbral dysfunction occur with subarachnoid hemorrhage?
increased intracranial pressure and poorly understood toxic effects of subarachnoid blood on brain tissue and cerebral vessels
most common subarachnoid hemorrhage?
rupture of berry aneurysm (congenital weakness in the walls of large vesssls at the base of the brain)
acute elevations in blood pressure or a variety of disorders that weaken vessels - resultant hematoma causes a focal neurologic deficit by compressing adjacent structures
in hypertensive patients - in walls of small penetrating arteries - major sites of rupture (small vessels that are involved in lacunar infarction) - basal ganglia and thalamus most common - also pons and cerebellum
what are causes of intraparenchymal hemorrhage?
charcot-bouchard aneurysms, vascular malformations, brain tumors (esp gliobastoma multiforme), platelet and coagulation disorders, cocaine and amphetamines (increase in BP)
cerebral amyloid angiopathy
alzheimer's - deposition of amyloid weakens the walls of small cortical vessels and causes lobar hemorrhage