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Neurobiology lectures II (FINAL EXAM)


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Ionic makeup of endolymph
high K+ and Ca++
What do hair cells stick into: endo or perilymphh
What structure marks the tall end of a hair bundle
What else besides the kinocilium compromises the hair bundle
about 30 "stereocilia", which aren't really cilia but are actin-filled projections.

30 stereocilia are arranged like a staircase
what is the kinocilium made of? the stereocilia?
kinocilium: MT
stereocilia: Actin
What connects the tips of stereocilia?
tip links
what are hair cells dervied from?
Movement of hair bundles in which direction will cause increased firing of 8th nerve fiber?
Movement toward KINOCILIIUM (this stretches tip link...)
"How did we know that auditory transduction is mechanicotransduction and not chemotransduction?
It is so fast. cf phototransduction, which is much slower.
How are hair channels opened mechanically?
bending toward kinocilium stretches tip links. this physically opens ion channels on the stereocilia...
What is going on whe hair cells are straight up?
Still some level of strech inducced transduction...about 15% of the strech-linked channels are open. tonic release of NT.
What happens ionically when strech channnels open?
Hi K+ and Ca++ from the endolymph flows into the hairs.
What does this ion flow do?
+ flow into cell. this depolarizes it.
Which ions pass thru stretch channel? Why?
K+ mainly
Ca++ also
and also Na+

Any cation, basically, will flow in via its electrochemical gradient. not a selective channel.
What is Meniere's syndrome?
vertigo attacks
fulneess in ear
eventual hearing loss

dilation/rupture of membranous labyrinth
How do strech channels adapt to continued stimulus?
Channel attached to myosin motor that asociates with actin core of the sterocilia.

With continued open stimulation, Ca influx causes Myosin motor to move downward. This relaxes tension in tip fiber, and stretch activated pores close.

The opposite happens with continued bending of hairs away from kinocilium. Myosin goes up shaft, taking up the slack in the tip fibers
What are the divisions of heriditary deafness?
1) syndromic: associated with other problems
2) nonsyndromic: only hearing problems
Name a genetic cause of hereditary deafness:
mutations in several unconventional myosins.
What are the major causes of hair cell loss?
1) hereditary defects
2) infections
3) ototoxic drugs (streptomycin,etc)
4) accoustic trauma
5) presbyacusis
How can some ototoxic drugs cause hearing loss?
They can plug the stretch-activated channels in the stereocilia
What general category of drugs is ototoxic?
aminoglycoside antibiotics
What is TTS?
Temporary threshhold shift

Temporary hearing loss after continued exposure to loud sounds

may be due to breakage of tip links, which can regenerate somewhat over a period of hours
where are the hair cells that mediate balance?
In the otolith organs and the semicircular canals
What do hair cells in otolith organs detect?
Static head position
Linear acceleration
What do hair cells in semicurcular canals detect?
They mediate dynamic head movement by detecting angular acceleration
how is utricle oriented
Hair cells pointing straight up
horizontal-oriented macular plane
How is saccule oriented?
vertical oriented macular plane
Where are hair cells/receptors in the semicircular canals?
on the ampullary crest
what is the cupula?
The elatinous mass that hair undles from duct hair cells project into, in the ampullae of the semicircular ducts
what is the relationship between dB level and sound intensity?
every 20 sb = 10 fold increase in sound pressure
what db level does hair cell damage occur?
what is the normal human frequency hearing range?
20 to 20,000 Hz
Vowels and consonents: frequencies?
consonants: hi frequencies
Vowels: lo frequencies
Where does stapes press on inner ear?
oval window
what are the middle ear muscles? Fxn?
tensor tympani (malleus)

dampen vibration during loud soounds
what is otosclerosis?
bone proliferation of stapes at oval window...causes hearing loss
How do you know if you have conductive hearing loss instead of sensorineural hearing loss?
1) hearing loss at all frequencies
2) bone conduction intact
What is in the scala vestibuli?
What is in the scala media?
What is the organ of corti?
Neuroepithelium on the basal membrane in the cochlea

Consists of
1) inner and outer hair cells
2) gelatinous tectorial membrane
3) supporting cells
describe tonotopic nature of basilar mmembrane
each segment of the basilar membrane vibrates maximally at a diiscrete frequence, from low at the beginning (wider) to high frequency at the top.
how many rows inner and outer hair cells?
1 inner
3 outer
Describe ratio of inner and outer hair cells and their connection to cn VIII afferents
10 outer hair cells will converge on one nerve fiber

1 inner hair cell will converge on 10 nerve fibers

so most afferent within the nerve 90+% are carrying input from inner hair cells
which scala does wave go up? which one down?
Up the scala tympani, down the scala vestibuli
What specialized feature do outer hair cells have? what might it be involved in?
they have a membrane structure that actually allows them to contract. This may be the basis of otoaccoustic emissions.

It also exerts forces on the tectorial membrane that may increase sensitivity and tuning sharpness.
what is place coding?
It is how nerve cells at each segment on the basilar membrane are "tuned" to have their lowest firing threshhold when activated by a particular frequency. So while other frequencies can activate it, it must be much louder..

this tonotopic organization is maintained all the way thru the cortex.
what is phase locking?
At low frequencies (only), 8th nerve fibers will tend to fire at the same phase of each wave, precisely preserving frequency information (1 beat, 1 fire).

this is another way to code information, in addition to place coding (infering info based on WHERE the nerve is coming from)
How is amplitude of sound wave coded for?
Increase of tone and you recruit more fibers to fire (ones slightly off tune, since you are now above their threshhold?)
what are the 2 methods of sound localization? Which nucleus is involved with each?
1) compare difference of intensity in each ear. Lateral superior olivary comples.
2) compare difference in timing in each ear--which ear does sound reach first? Medial superior olivary complex.
What is inferior collocilus involved in?
sound localization
probably the beginning of sound identificatioon
which frequencies get tonotopicaly expanded territory in the cortex?
those in the speech range
Which has more surface area: cerebrum or cerebellum?
Which has more neurons: cerebrum or cerebellum?
tie (20 billion)
what kind of learning might the cerebellum be involved in?
describe the cerebellar plasticity/eye patch experiment
cut lateral rectus of one eye to weaken it. It is slower to track target. If you patch it and have person look to weakened side, ok eye is normal and patched damage eye undershoots. If you patch normal eye and have it look to target, damaged eye hits target but patched normal eye overshoots.

BUT: with time and recovery, there is recovery of the lost function when patching occurs.

SUGGESTION: cerebellum might be involved in learning needed to compensate for injury
Describe Friedrichs ataxia
Hereditary ataxia
Autosomal recessive
affects large neurons in spine

Progressive ataxia, especially of trunk
Nystagmus, weakness, spasticity, REDUCED DTR

Usually associated with an unstable GAA (glut) repeat in the FRATAXIN gene

Worse when passed from father--more repeat expansion
Describe SCA
Spinocerebellar atrophy

Autosomal DOMINANT
Loss of Purkinje cells (mainly)
Associated with CAG repeats in ataxin gene (a nuclear kinase)
Repeats and diseases:

GAA: Friedrichs ataxia

CAG: Spinocerebellar atrophy, Huntingtons

CGG: Fragile X

CTG: myotonic dystrophy
What is the function of the basal ganglia?
think of them as a traffic cop: gating multiple stimuli that might evoke a motor act. they decide which one goes when
What makes up the basal ganglia
Globus pallidus
Subtantia nigra
What parts of the cerebbral cortex project to the basal ganglia
just about all of it! BG must recieve info re senation, motivation, emotion in deciding how to gate impulses
Describe the 3 prominent neurotransmitters involved in basal ganglia connections
GABA: inhbitory
Glutamate: excitatory
Dopamine: excitatory
What do you call motor disorders related to problems in basal ganglia? What does this group inlcude?

Chorea (rapid flicking)
Bradykinesia (poverty of movement)
Rigidity, stiffness
Tremor at REST)
Where is the neuron loss in parkinsons disease:
pars compacta of the substantia nigra (dopamineric neurons)
What does dopamine agonsist help/not help in parkinsons:
Helps bradykinesia, rigidity, slow gate
Does not help tremor at rest
What does help PD tremor?
cholinergic ANTAgonists.
Describe 2 surgical interventions for PD
Pallidectomy (selective lesion of globus palllidus)

Lesion of thalamus

Transplant fetal dopaminergic neurons
Describe pathophysiology of huntingtons:
Degeneration of caudate and putamen
(enlargement of lateral ventriclles)
What does CAG code for
glutamiine. polyglutamine forms nuclear inclusions/is insoluble
what disease are lewy bodies associated with?
What is Werner's syndrome
accelerated aging due to DNA helicase defect
Which matter do you lose more of wiht age?
White > gray

atrophy more common than actual cell loss
What are 3 possible mechanisms of CNS atrophy?
1) compromised blood flow
2) Trophic factor deprivation
3) Free radicals
Estrogen and aging
seems to act as a neuro growth factor--increase dendritic spine number. But it turns out it may actually promote dementia wiht time
What might be the aging pacemaker

causes decreas in GHRH (GH release) and GnRH (estrogen release)
Define dementia
Multiple cognitive defects that SIGNIFICANTLY disrupt function
What are the major types of Alzheimers disease? Describe
1) sporadic. 80-90% of cases. Late onset. Weak genetic association.

2) familial. 10% cases. Onset before 60. Strong genetic association (1, 14, 21--downs!)
Where do you find amyloid plaques and tangles in AD?
Limbic system
Cerebral cortex
Are plaques and tangles sufficient to cause AD?
no. both are found in nondemented brains.
How do plaques form?
Abberant cleavage of APP leads to formation of bad A-beta fragment, which aggregate and form extracellular plaques
What are tangles?
Intra and extracellular neurofilament groups that include Tau protein in abnormal helical arrangments
what gene is involved in familial AD
presenilin, may have role in APP processing
what protein is implicated in sporadic AD?
Apo E.

Lipid transporter that is found in amyloid plaques. Normal apoE may be required for Tau stabilization; abberrant apoE leads to tangle formation
Which apoE allele is the bad one for sporadic AD?
what 3 events are required for regeneration
1) replacement of lost neurons
2) regrowth of lost axons
3) reformation of specific connections
Why is frog retinal neuron regrowth not really regeneratino?
It was not evolved to make frog more viable, and doesn't surve that purpose in the wild. this is just an artifact of a DEVELOPMENTAL adaptation
Where is theere constitutivve neuron proliferation in mammals?
granule cells

in olfactory bulb and dentate gyrus of hippocampal formation. Confirmed with labelling experiments on people just before they died.
what did the labelling of granule cells in mice in enriched/not enriched environment show?
In enriched environment, there is not necessarily more granule cell proliferation (not more labeled neurons). But there seems to be less turnover...that is, the rate of dying of those cells is decreased. Thus, the bassal regeneration rate is > death rate, and with time it appears that more granule cells are labeled.
Rat experiment of stem cells injected for parkinsons disease
50% had symptom alleviation
20% had metastatic tumors

(there WAS differentiation of stem cells into neurons and glial cells)
What is nogo?
protein expressed in white matter of CNS. Seems to have something to do with why in CNS, the oligodendrocyte environment seems to inhibit axonal regrowth. If you add nogo antibodies, you can induce some axonal growh from nicked axon. These block the inhibitory epitopes on CNS myelin
Describe regrowth of axons in the periphery
Unike in CNS, they do regrow. But even in PNS, Regeneration is not specific to the correct targets.
recovery in children
seems to be better. may actually be some "reorganization" type plasticity. You can reroute an intercostal nerve to arm after brachial plexus is ripped...

Over time, arm movement is not associated with respiration! Not clear if reorganization is at cord or cortex level.
do glia retain the ability to divide/
yes. and they do, especially in response to injury
Types of glia in the 2 NSs.
Schwann cells

ependymal cells
what happens to schwann cell if axon dies/
it becomes phagocytic. also secretes growth factors (NGF)
do schwann cells always myelinate
no, sometimes they can just "ensheath" the axon
describe the 2 classes of astrocytes
1) fibrous. long processes, mainly in white matter tracts
2) protoplasmic. veil-like processes, more in gray matter. they ENVELOPE SYNAPSES.
name 2 things astrocytic processes do
1) line the outer surface of brain and blood vessels to form glia limitans
2) ensheath neuronal cell bodies, unmyelinated axons, dendrites, nodes, and synapses
how are astrocytes coupled
gap jxns. capable of spreading ca, K, ATP
What happens to astrocytes after injury in CNS
become phagocytic, may proliferate and form a glial scar
describe ependymal cells
1) line surfaces of ventricles
2) have cilia and microvili
3) LACK tight jxns, so CSF can equilibrate with ISF around brain tissue
4) specializes ependymal cells in choroid plexus secrete CSF
what are microglia
resident macrophages of CNS
how are microglia arranged in cns
spaced apart somewhat regularly, unlike the neurons that are all tangled together
what is the major site of HIV replication in the brain

can cause dementia
what kind of channels are at nodes?
how do glial cells buffer?
they act as a sink for extracellular K. They are permeable to K (almost exclusively), and they are connected by gap jxns to form a functional syncytium. so they are an infinite sink for excess K
How do glia function in neurotransmission
1) they themselves cannot propogate an AP
2) they can insulate synaptic inputs
3) they can uptake NT
4) they can also release some modulating NT into the synapse
Glia and NMDA receptors
can release D-serine, needed before NMDA receptors can respond to glutamate.
can Glial cells even modulate the NMJ
YES! injection of stimulatory subunit of G protein in a perisynaptic schwann cell caused decline in effected postsynaptic current after excitation!
What happens when you add glutamate around astrocytes?
you see propogation of intracellular Ca waves through the astrocyte syncytium
where are most CNS tumors derived from?
name the monaminergic neurotransmitteres
1) dopamine
2) epineprine
3) norepinephrine
4) serotonin
5) histamine
Name the catecholamines
Describe Catecholamine synthesis
1) starts with TYROSINE
2) Tyr hyroxlyase makes L-DOPA
3) DOPA decarboxylase --> dopamine
4) Dopamine hydroxylase --> NE
5) NE demethylation: Epinephrine
Serotonin sytnethesis
1) starts with TYPTOPHAN
2) Tryp hydroxlase --> 5-HTP
3) 5-HTP decarboxylase --> serotonin
Histamine synthesis
HISTIDINE --> Hist decarboxlyase --> HISTAMINE
What causes release of monoamine containing vesicles from terminal?
Ca+ influx
What are most monoamine receptors?
most are g protein-coupled
How are monoamines dealy with after release
1) degredation on postsynaptic terminal (COMT)
2) active semi-selective reuptake (NET, SERT, DAT)
3) ...followed by degradiation in presynaptic terminal by MAO
4) or reloading into vesicle by vesicle surface VMAT
Where does the dopaminergic system project from and to?
FROM: substantia nigra/ventral tegmental area of midbrain

1) Nigrostriatal
2) Mesolimbic (amygdala, hippocampus, cingulate).
3) mesocortical
describe more the 3 components of the dopaminergic system
1) nigrostriatal. Project to C/P (striatum). PArkinsons path
2) mesolimbic. Ventral tegmental midprain to limbic system. Reward pathway
3) mesocortical. Ventral tegmental midbrain to prefrontal cortex. Schizophrenia?
Describe location of noradrenergic system
1)STARTES: locus coeruleus in brainstem

2) PROJECTS: widely. Has to do with depression....
Describle location of histaminergic system
1) originates in TUBEROMAMILLARY NUCLEUS of hypothalamus.

2) PROJECTS: sparsely but widely. Involved in arousal and attention. Affected by benadryl, which crosses blood brain barrier.
How do amphetamines and cocaine work?
alter catecholamine levels by blocking reuptake of monoaminergic NT
What might cause depression?
downregulation of monoamines, esp catecholamines and serotonin
Describe treatments for depression
1) MAO inhibitors. Bad side effects. stop breakdown of monoamines
2) tricyclic antidepressents: block reuptake of monoamines
3) SSRI: selectively block reuptake of serotonin
4) ECT: effective 85% of the time!

NOTE: remember that psychological effects occur several weeks after the action of the drug starts!
What treats bipolar disorder/
Is schizophrenia usually associated with violent behavior?
Name some anatomical changes associated with schizophrenia
enlarged ventricles
widening of sulci/brain atrophy
decreased activityy in prefrontal cortex
What is a theory of what causes schizophrenia?
excess dopamine. So many antischizophrenia drugs are dopamine receptor antagonists (HAldol, etc)
Which dopaminergic system is associated wiht schizophrenia?

Mesolimbic: drug addiction
Nigrastriatal: parkinsons...
side effect of clozapine:
weight gain
What are some side effects of antipsychotic drugs (dopamine antagonists)
1) parkinsonism
2) acute dystonia (spasms)
3) tardive dyskenesia (stereotyped involuntary movements of the mouth that show up later)
Is consciousness a function of sensory input?
no. If you cut off all sensory input,, you still have sleep wake cycles
what structure maintains consciousness?
Reticular formation, a loose aggregation of cells extending from medulla to midbrain
what are the main functions of the reticular formation?
1) regulate respiration and heart fxn
2) maintain wakefulness
3) regulate sleep
How does REM sleep amount change with age?
declines wiht age. Fetuses have mostly REM sleep. With age amt of rem sleep declines
What structures do slow wave and REM sleep depend on?
REM: raphe nucleus (serotonergic)

Slow wave: locus corrueleus (noradrenergic)
What happens with "real" rat slleep deprivation?
body weight goes down
Food intake goes up
What regulates motor inhibition in REM sleep?
locus corueleus in the pons
inheritance pattern of narcolepsy.
autosomal recessive
gene codes for "orexin"
What all is orexin associated with?
diminished orexin in CSF associated with narcolepsy with cataplexy

increased orexin levels associated with food deprivation (hunger signal)

inject orexin in animals-->increased eating, obesity, reduced sleep

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