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neuro > Unit 1 > Flashcards

Unit 1 Flashcards

1
Q

Define cortex

A
  • outer layer of the cerebrum made of folded grey matter
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2
Q

Define grey matter

A
  • cell bodies and dendrites
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3
Q

Define white matter

A
  • axons
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4
Q

Define thalamus

A
  • made of grey matter (cell bodies)
  • acts as relay center to transmit info to cortex
  • different nuclei corresponding to different inputs and outputs
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5
Q

Define cerebellum

A
  • coordinates muscular activity
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6
Q

Define ipsilateral

A
  • on the same side as
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7
Q

Define contralateral

A
  • on the opposite side of
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8
Q

Define commissure

A
  • band of nerve tissue connecting the hemispheres of the brain
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9
Q

Define decussation

A
  • where nerve fibers cross from one lateral side to the other
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10
Q

Define homunculus

A
  • the map of areas in the cortex that correspond to a representation of th body where certain areas, like the hands and face, are overrepresented in the cortex
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11
Q

Define somatotopy

A
  • areas of the brain, when stimulated, correspond to movement in a particular part of the body in a mapped sort of fashion
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12
Q

Define afferent

A
  • fibers carrying information TO the cell body (dendrites) or CNS
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13
Q

Define efferent

A
  • fibers carrying information AWAY/EXITING the cell body (axon) or CNS
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14
Q

Define synapse

A
  • the point of transmission of info between neurons

- mediates communication between neurons

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15
Q

Define synaptic plasticity

A
  • neurons that fire together wire together
  • when an axon in cell A is near enough to excite cell B and repeatedly and persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficacy in firing B is increased”
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16
Q

Describe the basic conceptual framework for understanding the nervous system

A
  • neurologic exam
  • anatomic localization
  • neuropathology
  • gene expression makes neurons and activity of neurons modifies gene expression
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17
Q

Describe the basic components of the neurologic exam, neuroanatomical localization, and neuropathological categories and how these are employed in the formulation for a differential diagnosis

A
  • neurologic exam: being able to detect signs of neurologic abnormalities in a patient
  • neuroanatomical localization: being able to deduce from the abnormality where the damage or lesion or whatever may be in the nervous system
  • neuropathology: putting everything altogether and backwards and recognizing classic presentations
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18
Q

Recognize the relationship between the conceptual framework for the course and the 3 categories of therapeutic intervention for disorders of the nervous system: behavioral therapies, pharmacotherapies, and physical interventions

A
  • these different therapies share a mechanism of action broadly
  • they all produce lasting functional changes in the circuity of the nervous system that underlies the behavior
  • these therapies exert effects on behavior by modulating the elements of the nervous system that underlie behavior
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19
Q

Cajal and the Neuron Doctrine

A
  • the neuron is a distinct anatomic and physiologic unit that transmits info in the nervous system
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20
Q

For each of the following, identify which is gray matter and which is white matter: nucleus, lemniscus, ganglion, peduncle, cortex, funiculus, body, fasciculus, tract.

A
  • nucleus: grey
  • lemniscus: white
  • ganglion: grey
  • peduncle: white
  • cortex: grey
  • funiculus: white
  • body: grey
  • fasciculus: white
  • tract: white
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21
Q

Describe the function and distribution of each of the following cell types: astrocyte, microglia, oligodendrocyte, Schwann cell.

A
  • functions to buffer K, recycle NTs, nutrient support, myelination, involved in the BBB, supplies growth and trophic factors
  • microglia: phagocytic; clear tissue in response to damage
  • oligodendrocytes: form myelin in the CNS
  • Schwann cells: from myelin in PNS and only around one axon
  • astrocytes: maintain ionic equilibrium; removes NTs from extracellular space/synapse for recycling; control of nutrients from blood to neuron and control of blood flow
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22
Q

Describe the general function of each of the following parts of a neuron: dendrite, axon, axon terminal, Nissl substance.

A
  • dendrite - receives APs from pre-synaptic neurons; transmits signal to cell body; passive conductor
  • axon: has voltage sensitive ion channels to propagate APs
  • axon terminal - where one neuron transmits the signal to the next neuron through a synapse
  • Nissl substances/bodies - collections of rough endoplasmic reticulum stacked upon each other; lots of protein production
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23
Q

Describe the relationship between cerebral blood flow and fMRI and PEt scans.

A
  • inc in neuronal activity –> inc in local blood flow
  • fMRI utilizes Hb and PET utilizes tracer
  • neurons generate NO which dilates blood vessels
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24
Q

Discuss why substances in the circulatory system do not freely enter the brain parenchyma.

A
  • capillaries of the brain are not fenestrated (endo cells don’t have spaces between them)
  • must diffuse through endo cells if lipid-soluble or be actively transported
  • can prevent toxins from entering, but can also prevent drugs from acting
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25
Q

Describe how astrocytes can regulate local blood flow in proportion to the neuronal activity in the area.

A
  • communication between astrocytes and endo cells
  • astrocytes form a dense network among neurons and have foot processes that connect to vessel walls
  • these foot processes bring nutrients to neurons and regulate vessel function
  • when astrocytes take up glutamate –> release of arachidonic acid in astrocyte –> astrocytes have a P450 enzyme that acts on AA to form EET –> acts on arterioles to hyperpol membrane –> dec vascular tone
  • essentially: inc neuronal activity –> inc glutamate uptake –> inc EET release –> hyperol of vessel wall –> dec vascular tone –> inc diameter –> inc blood flow
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26
Q

Describe the differences in neural regeneration and glial response comparing the peripheral and central nervous systems.

A

PNS:

  • Schwann cells react to damage by clearing myelin debris and then line along endoneurium to allow the growth cone to move in that direction
  • microglia and astrocytes are activated
  • microglia strip synapses and cause reorganization

CNS:

  • oligodendrocytes do not clear myelin debris and do not form a pathway for elongation
  • up-regulate molecules that inhibit axonal growth
  • microglia and astrocytes activate to form a glial scar to prevent regeneration
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27
Q

What is the difference between ionotropic and metabotropic receptors for NTs?

A
  • if NT binds to an ionotropic receptor –> receptor changes conformation to allow ions through –> depol or hyperpol
  • if metabotropic receptor –> second messenger systems (G proteins) are activated and causes a local biochemical cascade –> change membrane conductance
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28
Q

Autoregulation in brain arterioles

A
  • BP inc –> inhibition of KCa channels –> depol and Ca influx –> activation of muscle in wall –> constant vessel diameter
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29
Q

Trace the path a corpuscle might take from the internal carotid artery to somatosensory cortex to the jugular vein. Does it matter whether it is the “foot” or “hand” region of somatosensory cortex?

A
  • internal carotid –> medial cerebral artery –> somatosensory cortex –> superior sagittal sinus –> transverse sinus –> sigmoid sinus –> jugular vein
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30
Q

How might blood from the left vertebral artery reach the frontal lobe of the right side in case of occlusion of an internal carotid artery?

A
  • left vertebral artery –> basilar artery –> posterior cerebral –> posterior communicating –> anterior cerebral
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31
Q

Draw and label the components of the circle of Willis

A
  • anterior communicating (north)
  • posterior communicating (east and west)
  • internal carotids (NE and NW)
  • posterior cerebral (south)
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32
Q

Describe the difference in physical relationships between the CNS, layers of the meninges, and the bone, comparing the situation in the cranium to that for the spinal column

A
  • pia: single layer not separable from brain surface
  • subarachnoid space: filled with CSF
  • arachnoid: loose and spongy
  • dura: leathery that is closely applied to cranium and hangs loosely from spinal column
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33
Q

Trace the path of CSF from its place of formation in the lateral ventricles to its site of resorption in the arachnoid granulations

A
  • lateral ventricles –> interventricular foramen –> third ventricle –> cerebral aqueduct –> fourth ventricle –> subarachnoid space –> arachnoid granulations in dural sinuses
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34
Q

Describe the relationship between ependymal cells and capillaries in the choroid plexus and how CSF is formed by this structure. Approximately, what is the volume and rate of production of CSF? Describe what happens to the composition of CSF as the ionic composition of plasma changes?

A
  • ependymal cells are tightly together with tight junctions
  • capillaries lose their tight junctions so solutes and nutrients can diffuse out of caps and across ependymal cells with active transport to get into CSF
  • brain and spinal cord float in about 125mL of CSF with ~100mL in the subarachnoid space
  • 500mL of CSF is produced each day
  • it is tightly regulated so neuron potentials are not affected
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35
Q

Distinguish between communicating and non-communicating hydrocephalus

A
  • non-communicating: if flow of CSF is interrupted by obstruction of an interventricular foramen or of the cerebral aqueduct
  • communicating: if CSF gets to subarachnoid space but is not being resorbed properly
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36
Q

What does the internal carotid artery supply in the brain?

A
  • anterior half of brain including entire cerebral hemisphere EXCEPT for medial occipital lobe and inferior temporal lobe
  • ICA –> anterior cerebral arteries –> ant medial 2/3 frontal and parietal
  • ICA –> medial cerebral arteries –> lateral frontal, parietal and temporal; penetrating branches –> white matter (susceptible to strokes)
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37
Q

What do the vertebral arteries supply in the brain?

A
  • brainstem, cerebellum, medial occipital lobe and inferior temporal lobe
  • VA –> basilar artery (pons)–> posterior cerebral arteries (midbrain, medial occipital and inferior temporal)
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38
Q

What are the 3 layers of meninges from innermost to outermost?

A
  • pia, arachnoid, dura
  • pia: single layer not separable from brain surface
  • subarachnoid space: filled with CSF
  • arachnoid: loose and spongy
  • dura: leathery that is closely applied to cranium and hangs loosely from spinal column
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39
Q

Review the differences between and EPSP, IPSP, and an action potential

A
  • EPSP: postsynaptic potential that makes it likely for it to fire an AP
  • IPSP: postsynaptic potential that makes it less likely to fire an AP
  • AP: a transient increase in the membrane potential of a cell usually to transmit information in a direction
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40
Q

Describe the “coupling” between electrophysiologic activity in the nervous system and CNS hemodynamics

A
  • neurons general electromagnetic potentials as a way of transmitting information and the more active neurons require increased blood supply to those areas
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41
Q

Describe those techniques for evaluating “brain activity” that measure the electromagnetic properties of the nervous system

A

Electroencephalogram (EEG):

  • measures electrical potential fluctuations at scalp
  • these fluctuations are produced by temporal and spatial summation of electrical currents caused by slow EPSPs and IPSPs in the neurons of the cerebral cortex
  • pyramidal neurons receive similar inputs and cause potential changes that sum in the EC space that penetrates CSF –> potential differences in scalp

Event Related Potential (ERP):

  • pattern of positive and negative peaks that occur after the repeated delivery of a stimulus
  • EEGs repeated and averaged over time

Magnetoencephalogram (MEG):

  • measures small magnetic fields induced by electrical current flux
  • samples dipoles with a different orientation than EEG
  • measures populations of neurons like EEG

Electromyography (EMG):

  • electrodes in skeletal muscle and recording membrane potentials
  • usually done while stimulation peripheral nerve
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42
Q

Describe those techniques for evaluating “brain activity” that measure the hemodynamic properties of the nervous system

A

Functional MRI (fMRI):

  • detects changes in deoxyhemoglobin which is paramagnetic and causes distortion in magnetic fields
  • changes in deoxy to oxy ratios –> measurable change in MR signal
  • diffusion weighted imaging (DWI) shows diffusivity of H2O molecules and detects early ischemia, MS, trauma, and brain tumors
  • diffusion tensor imaging (DTI) allows in vivo examination of tissue microstructure
  • DTI calculates fractional anisotropy and can image white matter pathways

Positron Emission Tomography (PET):

  • inject tracer with positron-emitting radionuclide
  • decays into photons that are detected
  • reconstruct decayed particles
  • subtract control from stimulation
  • H215O can measure cerebral blood flow, 18FDG can measure glucose metabolism, 18FD can show where dopamine conversion is max

Single Photon Emission Computed Tomography (SPECT):
- won’t go into

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43
Q

Describe at a basic level the method of Diffusion Tensor Imaging (DTI)

A
  • diffusion tensor imaging (DTI) allows in vivo examination of tissue microstructure
  • DTI calculates fractional anisotropy and can image white matter pathways
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44
Q

Describe at a basic level the objective of “Connectomics.” Understand the potential for this technique to act as a biomarker for certain disease states.

A
  • nodes are neurons and the edges/pathways are synapses between neurons
  • map of structural relationships within nervous system
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45
Q

Describe EEG

A

Electroencephalogram (EEG):

  • measures electrical potential fluctuations at scalp
  • these fluctuations are produced by temporal and spatial summation of electrical currents caused by slow EPSPs and IPSPs in the neurons of the cerebral cortex
  • pyramidal neurons receive similar inputs and cause potential changes that sum in the EC space that penetrates CSF –> potential differences in scalp
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46
Q

Describe ERP

A

Event Related Potential (ERP):

  • pattern of positive and negative peaks that occur after the repeated delivery of a stimulus
  • EEGs repeated and averaged over time
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47
Q

Describe MEG

A

Magnetoencephalogram (MEG):

  • measures small magnetic fields induced by electrical current flux
  • samples dipoles with a different orientation than EEG
  • measures populations of neurons like EEG
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48
Q

Describe EMG

A

Electromyography (EMG):

  • electrodes in skeletal muscle and recording membrane potentials
  • usually done while stimulation peripheral nerve
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49
Q

Describe fMRI

A

Functional MRI (fMRI):

  • detects changes in deoxyhemoglobin which is paramagnetic and causes distortion in magnetic fields
  • changes in deoxy to oxy ratios –> measurable change in MR signal
  • diffusion weighted imaging (DWI) shows diffusivity of H2O molecules and detects early ischemia, MS, trauma, and brain tumors
  • diffusion tensor imaging (DTI) allows in vivo examination of tissue microstructure
  • DTI calculates fractional anisotropy and can image white matter pathways
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50
Q

Describe PET

A

Positron Emission Tomography (PET):

  • inject tracer with positron-emitting radionuclide
  • decays into photons that are detected
  • reconstruct decayed particles
  • subtract control from stimulation
  • H215O can measure cerebral blood flow, 18FDG can measure glucose metabolism, 18FD can show where dopamine conversion is max
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51
Q

What is the mechanism of the AP and what is the Nernst equation?

A
  • a depolarization of the cell membrane leads to an influx of positive ions that propagate down the axon of the neuron
  • the nernst equation is:

VEq = (RT/zF)*ln([X]o/[X]i)

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52
Q

What is the electrical synaptic transmission? Name a limitation of this form of intercellular communication (compared to chemical transmission). Why would it be ineffective at the NMJ? Is this method of communication important in the mammalian CNS? Name examples of electrical synaptic transmission

A
  • an electrical synapse is the transmission of the depolarized membrane potential directly to the postsynaptic neuron without using the synaptic cleft
  • without chemical transmission there is no amplification –> can’t provide the necessary 30mV to reach threshold and as a result would not be able to transmit the AP along the large muscle fiber
  • electrical connections are seen in the heart
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53
Q

Name the presynaptic events involved in transmitter release, from the time of the arrival of an action potential to exocytosis. Describe the subsequent presynaptic events involved in cleanup operations, both outside the cell (consider the neurotransmitter molecules) and inside the cell (consider sodium ions, calcium ions, synaptic vesicles, and neurotransmitter).

A
  • AP arrives at presynaptic terminal –> depol causes voltage gated Ca channels to open –> Ca enters cell and causes fusion of vesicle membrane with cell membrane –> NTs are released into synaptic cleft
  • NT clean up happens by 3 mechanisms:
    1) NTs diffuse out of cleft into ECF
    2) NTs are recycled and pumped back into presynaptic terminal by astrocytes
    3) NTs are destroyed like by ACh esterase
  • vesicle is recycled and remade and refilled with NTs
  • Ca ions will be pumped out of cell (ATP pump and a Na/Ca exchanger)
  • vesicles reformed by kiss and run and clathrin endocytosis
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54
Q

How does tetanus toxin act?

A
  • binds to peripheral nerve terminals
  • fixes to gangliosides at the presynaptic inhibitory motor nerve endings –> taken up by nerve
  • ultimate effect is to block release of inhibitory NTs (glycine and GABA) across synapse –> inhibition of inhibition means more excitation –> generalized muscle spasms and constriction
  • acts by cleaving protein component of synaptic vesicles (synaptobrevin II) and this stops release of inhibitory NTs
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55
Q

How does botulinum toxin act?

A
  • prevents release of ACh across synapse
  • toxin forms a channel through membrane of neuron and receptor endocytosis –> inhibit ACh release probably though proteolytic cleavage of synaptobrevin II –> neurons can’t release ACh –> paralysis of motor system
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56
Q

Describe how the neuromuscular synapse amplifies the incoming signal in order to depol the muscle fiber to threshold for an AP

A
  • electrical signal becomes a chemical one with ACh as a NT
  • each vesicle has several thousand ACh molecules that can activate 1000+ postsynaptic ACh receptors
  • exocytosis releases up to 100 vesicles that each produce about a 1mV depol
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57
Q

What is the safety factor at the NMJ? Do CNS synapses have safety factors as well? Why/why not?

A
  • the safety factor is the fact that a lot of vesicles are secreted in order to ensure transmission of the AP
  • CNS does not have it as much because CNS is more involved in info processing so you may or may not want certain neurons to fire and propagate APs
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58
Q

Define facilitation and synaptic depression of transmitter release. Name the underlying mechanism of each.

A

Synaptic facilitation:

  • Ca ion concentration builds up during high freq stimulation
  • number of vesicle secreted inc because more Ca present
  • lasts .1 seconds (the time it takes to pump out Ca ions that leaked in)

Synaptic depression:

  • cannot replenish vesicles quickly enough
  • not enough NT released over time
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59
Q

Describe the three mechanisms for removing transmitters from synaptic clefts

A

NT clean up happens by 3 mechanisms:

1) NTs diffuse out of cleft into ECF
2) NTs are recycled and pumped back into presynaptic terminal by astrocytes
3) NTs are destroyed like by ACh esterase
- vesicle is recycled and remade and refilled with NTs

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60
Q

What is a MEPP?

A
  • Miniature End Plate Potential

- they are due to the spontaneous, simultaneous secretion of a single synaptic vesicle filled with ACh

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61
Q

Describe the basic mechanism that determines whether a synapse is direct (fast) or indirect (slow). Name a typical physiological response mediated by each

A

Fast:

  • postsynaptic potentials turn on and off in a few milliseconds
  • NTs bind to receptors and instantly change postsynaptic membrane permeability
  • direct

Slow:

  • NT receptor is not an ion channel
  • it is a transmembrane protein that undergoes a structural change when the NT binds –> G protein senses change and leads to ion channel behavior change elsewhere
  • indirect because it uses secondary messengers to send signals
  • advantages: secondary messengers last longer in cytoplasm than NTs in synaptic cleft –> can last for long time after NTs are gone
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62
Q

Describe the conductance (permeability) characteristics of the channel opened in the fast excitation. Define the electrical “driving force.” Define the reversal potential for direct excitation

A
  • the channels opened in fast excitation are NSC (Non-Selective Cation) channels –> which is permeable to Na and K so the reversal potential is around -10mV (still above threshold)
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63
Q

Describe the kind of channel that is opened during fast inhibition in the CNS

A
  • GABA is the most common inhibitory NT –> causes an inc in Cl permeability in the postsynaptic membrane –> inhibition
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64
Q

Why is the inhibition often more powerful than one might predict from the size of an individual IPSP?

A
  • this is because the membrane potential is determined by the relative permeabilities of ions
  • a smaller IPSP can cause a larger permeability change
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65
Q

Define temporal and spatial summation of postsynaptic potentials

A

Spatial summation
- multiple excitatory synaptic inputs on a neuron firing an AP simultaneously –> drives postsynaptic membrane potential toward threshold for an AP

Temporal summation

  • single excitatory input stimulated multiple times in succession
  • each succeeding input made before the previous one decays –> see effect of temporal summation and facilitation
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66
Q

What is a coincidence detector? How does the NMDA receptor work as a coincidence detector? How can activation of NMDA receptors lead to synaptic strengthening? How might such a mechanism lead to behavioral associative conditioning?

A
  • NMDA receptor
  • excitatory synapse with glutamate as NT
  • AMPA receptors are like ACh receptors at NMJ (NSC channels opened by glutamate)
  • NMDA are similar but they bind glutamate and also the pore is plugged by Mg and have a high permeability to Ca ions
  • needs two events to happen at the same time to conduct: presynaptic activation leads to ligand gate opening by glutamate and also need a postsynaptic AP/depol to pop Mg out of pore
  • Ca through NMDA channel can insert AMPA receptors in postsynaptic membrane –> inc size of glutamate-induced synaptic potentials –> strengthened synapse
  • Ca ions also cause NO to go back to presynaptic cell and potentiate NT release
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67
Q

What is LTP? What is LTD? How are they involved in learning and memory?

A

LTP:

  • long term potentiation
  • some CNS neurons have associative plasticity –> become potentiated not just with own activity but when their own activity is combine with a unique signal from the postsynaptic cell
  • requires burst of high frequency stimulation

LTD:
- long term depression
- low frequency stimulation causes smaller synaptic responses
- may involve endocytosed AMPA receptors from postsynaptic membrane –> dec sensitivity to glutamate secreted by presynaptic terminal
-

68
Q

What is the major inhibitory NT in the CNS?

A

GABA

- acts by inc Cl permeability in the postsynaptic membrane

69
Q

List the precursors and key enzymes for the synthesis and transporters involved in the storage of ACh, monoamine (DA-NE-5HT), and amino acid transmitters (GABA-Glu)

A

ACh:

  • acetyl CoA + choline (via choline acetyl transferase) –> ACh + CoA
  • ACh is taken up into vesicles and packaged for release

Monoamines:

  • NE and DA: rate limiting enzyme is tyrosine hydroxylase (tyrosine –> LDopa –> DA –> NE)
  • 5HT: rate limiting enzyme is tryptophan hydroxylase (tryptophan –> 5-OH-tryptophan–> 5HT)
  • taken up into vesicle via vesicular monoamine transporter (VMAT) –> packaged and protected by monoamine oxidase (MAO)

GABA:

  • intertwined with synth of glutamate via GABA shunt; glutamate via GAD
  • Glutamate –> GABA (via GAD) –> Glutamate (via alphaKG) –> Glutamine (via GluSyn) –> Glutamate (via Glutaminase)

Glu:

  • formed from glutamine by glutaminase
  • glutamate reenters the neuron via a neuronal glutamate transporter or by glial cells and converted to glutamine by GluSyn then taken into neuron and converted to glutamate by glutaminase
70
Q

Describe the synaptic mechanisms by which ACh, monoamine (DA-NE-5HT), and amino acid transmitters (GABA-Glu) are released and then inactivated at a synapse

A

ACh:

  • AP reaches nerve terminal through Na channels and this opens Ca channels –> Ca influx –> fusion of vesicle with membrane –> ACh exocytosed into synapse
  • terminated by enzymatic degradation by ACh esterase

Monoamines:

  • AP comes and opens Ca channels –> fusion of vesicles –> expulsion of monoamines into synapse
  • terminated by presynaptic membrane transporters (DAT for DA, NET for NE, SERT for 5HT) that take back NTs into nerve terminal –> can be inactivated by MAO or put into vesicles by VMAT

GABA:

  • terminate by reuptake into presynaptic neuron and glial cells
  • also a GABA transporter like monoamine reuptake transporters

Glu:

  • reenters via glutamate transporter or glial cell transporter
  • if in glial cell, converted to glutamine by glutamine synthetase –> taken up into neuron then converted to glutamine by glutaminase
71
Q

Describe the receptors and signal transduction systems for ACh, monoamine (DA-NE-5HT), and amino acid transmitters (GABA-Glu)

A

ACh:

1) muscarinic receptors:
- M1-M3: Gq –> stimulate PLC activity
- M2-M4: Gi/o –> inhibit adenylyl cyclase activity
2) nicotinic receptors:
- NN –> opens receptor-gated cation channels (ionotropic)

Monoamines:

1) NE:
- alpha1: Gq –> stim phospholipase C
- alpha2: Gi/o –> inh adenylyl cyclase and K channel opening
- beta1: Gs –> stim of adenylyl cyclase
- beta2: Gs –> stim of adenylyl cyclase

2) DA
- D1 DA receptor: Gs –> stim of adenylyl cyclase
- D2 DA receptor: Gi/o –> inh of adenylyl cyclase activity
3) 5HT
- 1A,1B,1D: Gi/o –> inh of adenylyl cyclase activity and open K channel
- 2A,2B,2C: Gq –> stim of PLC and close Ca channel
- 3: Ligand-gated cation channel –> excitatory (ionotropic)
- 4: Gs –> stim of adenylyl cyclase

GABA:

  • A: opens ligand gated Cl channel –> dec neuronal exc (IPSP) (ionotropic)
  • B: Gi/o –> inh adenylyl cyclase, dec Ca conductance, open K channel

Glu:

  • NMDA: inc Ca influx
  • AMPA: inc Na and Ca influx
  • Kainate: inc Na influx
  • R1-R5: Gq –> inc PLC activity
  • R2-R3: Gi/o –> dec AC activity, inh VSCC, activate K channels)
  • R4, R6-R8: Gi/o –> dec AC, inh VSCC)
72
Q

Develop an understanding of how pharmacologic agents can act to potentiate or decrease the activity of NT substances at a synapse by interfering with vesicular storage, by blocking uptake, by blocking metabolism, or by interacting with specific receptors for NT substances

A

yep

73
Q

Describe the role of ACh, monoamine (DA-NE-5HT), and amino acid transmitters (GABA-Glu) in hierarchical vs. diffuse neuronal systems

A

Hierarchical

  • motor and sensory
  • usually glutamate and GABA for exc and inh

Diffuse

  • modulate fcns of hierarchical systems
  • ACh and monoamines
74
Q

Where is GABA found?

A
  • high concentrations in the brain and spinal cord

- trace amounts in peripheral tissue

75
Q

What is the function of GABA?

A
  • major inhibitory NT in CNS
76
Q

Where is Glutamate found?

A
  • virtually all neurons in CNS

- highest in hippocampus, cortex, lateral septum, straitum, and cerebellum

77
Q

What is the function of Glutamate?

A
  • excitatory synapse transmission in CNS (AMPA receptors) and triggers neuroplasticity
78
Q

Where is ACh found?

A
  • brain stem and basal forebrain and widely projects to cortex and hippocampus
79
Q

What is the function of ACh?

A

coordinated movement and cognitive functions (memory, motivation, and learning)

80
Q

Where is DA found?

A
  • susbstantia nigra –> neostratum pathway, ventral tegmental area –> limbic cortex, ventral tegmental area –> frontal cortex pathway, hypothalamus –> pituitary
81
Q

What is the function of DA?

A
  • initiation of voluntary movement
  • reward-related behaviors
  • cognitive control of behaviors including working memory and control of attention
82
Q

Where is NE found?

A

pons and brainstem and projects to all levels of brain

83
Q

What is the function of NE?

A
  • regulation of arousal, attention, vigilance, sleep-wake cycle, fear response/anxiety, mood/emotion
  • descending pathways modulate afferent pain signals
84
Q

Where is 5HT found?

A

raphe region of pons/upper brain stem and projects to all levels of brain

85
Q

What is the function of 5HT?

A
  • sleep, arousal, attention, processing of sensory info in cortex
  • emotion and mood regulation, pain pathways
  • eating/drinking
86
Q

What is the function of 5HT?

A
  • sleep, arousal, attention, processing of sensory info in cortex
  • emotion and mood regulation, pain pathways
  • eating/drinking
87
Q

List the NTs and receptors that mediate neurotransmission at the ganglia and/or end organs in the parasympathetic and sympathetic nervous systems and the gross distribution of adrenergic and cholinergic receptor subtypes on these organ systems

A

Somatic NS:
- ACh is NT; released by efferent neurons and binds to nicotinic cholinergic receptors on voluntary skeletal muscle at NMJ

Parasympathetic NS:

  • pregang release ACh at ganglionic nicotinic cholinergic (NN) receptors
  • postgang release Ach at end organs’ muscarinic cholinergic (M1-5) receptors (heart, lungs, GI/GU, eye)

Sympathetic NS:
- pregang release ACh on ganglia and adrenal medulla nicotinic cholinergic receptors
-

88
Q

List the NTs and receptors that mediate neurotransmission at the ganglia and/or end organs in the parasympathetic and sympathetic nervous systems and the gross distribution of adrenergic and cholinergic receptor subtypes on these organ systems

A

Somatic NS:
- ACh is NT; released by efferent neurons and binds to nicotinic cholinergic receptors on voluntary skeletal muscle at NMJ

Parasympathetic NS:

  • pregang release ACh at ganglionic nicotinic cholinergic (NN) receptors
  • postgang release ACh at end organs’ muscarinic cholinergic (M1-5) receptors (heart, lungs, GI/GU, eye)

Sympathetic NS:

  • pregang release ACh on ganglia and adrenal medulla nicotinic cholinergic receptors
  • postgang release:
    1) NE at organs on alpha1, beta1, and beta2 receptors
    2) ACh at sweat glands on muscarinic cholinergic receptors
    3) DA at renal vascular smooth muscle on D1 receptors
  • adrenal medulla releases EPI and NE into general circulation that interacts with alpha1, beta1, and beta2 receptors
89
Q

Discuss the concept of “tone” and explain the consequence of the fact that parasympathetic tone predominates at most organs and tissues (exception being symp control of blood vessels)

A
  • balance between para and symp branches

- para is usually predominant except in control of vasculature (where there is no parasympathetic innervation)

90
Q

Describe homeostasis, flight or fight, and rest and digest with regard to symp and para activity

A

rest and digest

  • dec HR –> dec BP
  • stim GI motility and secretion –> inc nutrient absorption
  • empty bladder/rectum
  • pupil constriction

fight or flight

  • inc HR –> inc BP
  • blood flow from skin to skeletal muscles
  • inc blood glucose
  • dilate pupils
  • dec GI/GU activity
91
Q

List the NTs and receptors that mediate neurotransmission at the ganglia and/or end organs in the parasympathetic and sympathetic nervous systems and the gross distribution of adrenergic and cholinergic receptor subtypes on these organ systems

A

Somatic NS:
- ACh is NT; released by efferent neurons and binds to nicotinic cholinergic receptors on voluntary skeletal muscle at NMJ

Parasympathetic NS:

  • pregang release ACh at ganglionic nicotinic cholinergic (NN) receptors
  • postgang release ACh at end organs’ muscarinic cholinergic (M1-5) receptors (heart, lungs, GI/GU, eye)

Sympathetic NS:

  • pregang release ACh on ganglia and adrenal medulla nicotinic cholinergic receptors
  • postgang release:
    1) NE at organs on alpha1, beta1, and beta2 receptors
    2) ACh at sweat glands on muscarinic cholinergic receptors
    3) DA at renal vascular smooth muscle on D1 receptors
  • adrenal medulla releases EPI and NE into general circulation that interacts with alpha1, beta1, and beta2 receptors
92
Q

What are the effects mediated by muscarinic receptors at postganglionic effector organs?

A
  • CV: dec HR, dec AV, dec cont
  • vasodilation: indirectly through NO prod
  • resp: bronchoconstriction
  • GI: inc secretion, inc motility
  • GU: open sphincter, contract detrusor
  • eye: miosis (const), near vision, outflow of AH

DUMBBELSS

  • defecation
  • urination
  • miosis
  • bronchoconstriction
  • bradycardia
  • emesis (GI)
  • lacrimation
  • salivation
  • sweating
93
Q

What are the effects of sympathtic postgang synapses on organs?

A

Vasculature:

  • a1: vasoconst
  • B2: vasodil
  • D1 DA receptors cause relaxation in renal vasculature

Heart:
- B1: inc HR, inc AV, inc cont

Generally:

  • a1: vasoconstriction (inc BP –> dec HR reflex brady)
  • B1: inc HR and inc cont (inc BP)
  • B2: vasodilation (dec BP –> inc HR reflex tachy)
  • a2: dec SNS outflow –> dec BP
94
Q

What are the effects of sympathtic postgang synapses on organs?

A

Vasculature:

  • a1: vasoconst
  • B2: vasodil
  • D1 DA receptors cause relaxation in renal vasculature

Heart:
- B1: inc HR, inc AV, inc cont

Generally:

  • a1: vasoconstriction (inc BP –> dec HR reflex brady)
  • B1: inc HR and inc cont (inc BP)
  • B2: vasodilation (dec BP –> inc HR reflex tachy)
  • a2: dec SNS outflow –> dec BP

Kidney:
- inc renin release via NE acting on B1 receptors –> vasoconstriction and inc BP

Lungs:
- bronchodilation via B2

Eye:

  • mydriasis/dilation via a1
  • B2 causes inc AH prod

GI:

  • smooth muscle relax via alpha2
  • direct relax via B2
95
Q

What are the effects of sympathtic postgang synapses on organs?

A

Vasculature:

  • a1: vasoconst
  • B2: vasodil
  • D1 DA receptors cause relaxation in renal vasculature

Heart:
- B1: inc HR, inc AV, inc cont

Generally:

  • a1: vasoconstriction (inc BP –> dec HR reflex brady)
  • B1: inc HR and inc cont (inc BP)
  • B2: vasodilation (dec BP –> inc HR reflex tachy)
  • a2: dec SNS outflow –> dec BP

Kidney:
- inc renin release via NE acting on B1 receptors –> vasoconstriction and inc BP

Lungs:
- bronchodilation via B2

Eye:

  • mydriasis/dilation via a1
  • B2 causes inc AH prod

GI:

  • smooth muscle relax indirectly via alpha2
  • direct relax via B2

GU:

  • relax uterine smooth muscle via B2
  • contract ureteral sphincter via a1
  • relax bladder wall via B3
  • ejaculate via a1

Skeletal muscle:
- B2 causes tremors

Metabolic effects:

  • inc blood glucos via B2
  • inc lipolysis via B3
  • dec insulin secretion via a2
  • inc insulin via B2
96
Q

Describe the general mechanisms by which most drugs alter activity in the autonomic nervous system and compare and contrast the modes of drug action with respect to selectivity of action and clinical utility.

A
  • mimic NT action as an agonist
  • block NT action as an antagonist
  • change normal action of NT indirectly by altering:
    1) synthesis of NT
    2) storage/release of NT
    3) inactivate NT
  • greatest selectivity is with drugs that act postsynaptically
  • presyn drugs affect all synapses so less useful
97
Q

List the steps in the synthesis, storage, release and inactivation of acetylcholine, and drugs that affect these processes.

A

Synthesis/storage:

  • choline taken up by transporter with Na (blocked by hemicholinium)
  • AcCoA and choline make ACh
  • ACh stored in vesicles via VAT (inhibited by vesamicol)

Release:

  • influx of Ca –> vesicle exocytosis
  • blocked by botulinum toxin

Termination:

  • ACh esterase
  • AChE inhibito is an indirect cholinergic agonist
98
Q

For cholinergic receptors: a) list the locations of and the differences between nicotinic and muscarinic cholinergic receptors; b) describe the signal transduction mechanisms activated by stimulation of nicotinic versus muscarinic cholinergic receptors, and c) state the significance of presynaptic versus postsynaptic cholinergic receptors.

A

a)
nicotinic receptors:
- ligand-gated, change ionic permeability

muscarinic:

  • G protein coupled, alter enzyme activity
  • Gq –> inc PLC (M1: CNS and GI glands, M3: exocrine glands/smooth muscle)
  • Gi –> dec adenylyl cyclase (M2, M4: heart, CNS)`1
99
Q

How and where do cholinergic antagonists work?

A
  • act as reversible/competitive inhibitors at muscarinic receptors
  • selective at M1 (CNS, gastric parietal, symp post gang cells), M2 (cardiac), M3 (smooth muscle and glands)
100
Q

What are the alkaloid antimuscarinic drugs?

A

Atropine

Scopolamine

101
Q

What are the semisynthetic-synthetic antimuscarinic drugs?

A

Propantheline

  • quaternary ammonium
  • low lipid sol and poor oral abs

Benztropine

  • tertiary amine
  • CNS dist
102
Q

What are the semisynthetic-synthetic antimuscarinic drugs?

A

Propantheline

  • quaternary ammonium
  • low lipid sol and poor oral abs

Benztropine

  • tertiary amine
  • CNS dist
103
Q

How is NE synthesized and stored and inactivated?

A
  • tyrosine is precursor –> DOPA –> dopamine –> NE –> Epi
  • VMAT puts NE into vesicle where it is packaged and protected from degradation by MAO
  • release with Ca influx (blocked by bretylium)
    • reuptake of NE into nerve endigns by NET (80%)
  • NET inhibited by cocaine and tricyclic antidepressants
  • reverse NE through NET: amphetamines and pseudoephedrine
104
Q

How is NE synthesized and stored and inactivated?

A
  • tyrosine is precursor –> DOPA –> dopamine –> NE –> Epi
  • VMAT puts NE into vesicle where it is packaged and protected from degradation by MAO
  • release with Ca influx (blocked by bretylium)
    • reuptake of NE into nerve endigns by NET (80%)
  • NET inhibited by cocaine and tricyclic antidepressants
  • reverse NE through NET: amphetamines and pseudoephedrine
105
Q

How do alpha1 receptors work?

A
  • Gq protein –> activates PLC –> releases IP3 and DAG

- IP3 releases intracellular stores of Ca and DAG activates protein kinase C

106
Q

How do alpha2 receptors work?

A
  • Gi inhibits adenylyl cyclase activity –> dec cAMP levels or open K channels –> hyperpol –> coupled to Go and dec Ca movement
107
Q

How do beta1 and beta2 receptors work?

A
  • Gs protein that stimulates adenylyl cyclase –> inc cAMP synthesis –> activates protein kinase A catalytic activity
  • also inc Ca movement through LTCC
108
Q

How do direct acting adrenergic agonists work?

A
  • drug binds to adrenergic receptrs and makes same effects as NT would
109
Q

How do indirect acting adrenergic agonists work?

A
  • changes processing of NT
  • most commonly inc storage and release
  • drug is taken up by NET and transported into vesicles and displaces stored NE into cytoplasm; also reverses NET
  • antidepressants act by inhibiting NT reuptake from synapse
110
Q

What are the pharmacokinetics of NE and Epi?

A
  • not really effective orally and don’t enter brain well

- short

111
Q

How do anti-adrenergic drugs work?

A

1) Sympatholytic action:
- inhibit synthetic enzymes in presyn
- lack of specificity (all adrenergic synapses affected)
- Metryrosine (tyrosine hydroxylase)
- alpha-methyldopa (becomes a-methylNE which is an agonist at alpha2 receptors in CNS)
- Carbidopa (prevents dopamine formation)
- Disulfiram
- inhibit storage (Reserpine)
- inhibit release (Bretylium, Guanethidine)

2) block adrenergic receptors on postsyn
3) activate alpha2 receptors

112
Q

What are the alpha adrenergic receptor antagonists?

A

Non-selective:

  • Phentolamine (reversible)
  • Phenoxybenzamine (irreversible)

Selective:

  • Prazosin
  • Terazosin
  • Doxazosin
113
Q

What are the beta adrenergic receptor antagonists?

A

different affinities for B1 (heart) and B2 (lung/blood vessels)

Propranolol
- nonselective (B1 and B2)

Metoprolol/Atenolol
- B1 selective (heart)

114
Q

How does activation of alpha2 receptors work to be anti-adrenergic?

A
  • reduces symp NS activity
  • CNS: reduces peripheral SNS activity
  • SNS: dec NE release
  • Clonidine
115
Q

How does activation of alpha2 receptors work to be anti-adrenergic?

A
  • reduces symp NS activity
  • CNS: reduces peripheral SNS activity
  • SNS: dec NE release
  • Clonidine
116
Q

What are the direct acting cholinergic agonists?

A

Pilocarpine
Bethanechol
ACh
Nicotine

117
Q

What are the indirect acting cholinergic agonists?

A 
Neostigmine
Pyridostigmine
Edrophonium
Donepezil
Physostigmine
Organophosphate nerve gases
118
Q

What are the indirect acting cholinergic agonists?

A 
Neostigmine
Pyridostigmine
Edrophonium
Donepezil
Physostigmine
Organophosphate nerve gases
119
Q

Describe the primary axes of the central nervous system, and the designations dorsal, ventral, rostral, and caudal. Understand the planes of section used to view the nervous system

A
  • cephalic flexure: 80deg turn between diencephalon and mesencephalon (near thalamus)
  • rostral is toward face
  • caudal is toward back of head or tail
  • dorsal is toward head or back
  • ventral is toward spine or stomach
  • horizontal, coronal, and sagittal planes
120
Q

Describe the way in which the nervous system is segmented into rostrocaudal segments of telencephalon, diencephalons, mesencephalon, metencephalon, myelecephalon, and spinal cord

A
  • original segments are prosencephalon (forebrain), mesencephalon (midbrain), and rombencephalon (hindbrain)
  • prosencephalon –> diencephalon (thalamus, hypothalamus, subthalamus, and epithalamus; lumen becomes 3rd ventricle) and telencephalon (cerebral hem and lat ventricle)
  • mesencephalon stays mesencephalon (lumen becomes cerebral aqueduct)
  • rhomencephalon becomes metencephalon (pons and cerebellum) and myelencephalon (medulla); lumen becomes 4th ventricle
121
Q

Discuss the components of the ventricular system and how these relate to the rostrocaudal segments of the neural tube

A
  • telencephalon –> lateral ventricle
  • diencephalon –> third ventricle
  • mesencephalon –> cerebral aqueduct
  • rhombencephalon –> 4th ventricle
122
Q

Describe the significance of the rhombomeres, in terms of the segmental development of the hindbrain and its relationship to specific cranial nerves

A
  • rhombencephalon is made of 8 rhombomeres
  • r1 is just posterior to the mesencephalon
  • r8 is anterior to the spinal cord
  • r1 has trochlear oculomotor neurons originate
  • r5 and r6 have abducens oculomotor neurons
  • each segment has a different combo of Hox genes –> different programs of differentation
  • cranial nerve 5 –> r1, r2, r3
  • cranial nerve 7 –> r4, r5
  • cranial nerve 9 –> r6, r7
123
Q

Describe the general scheme of dorsoventral patterning of the neural tube into alar and basal plates, and how this scheme is modified at the level of the midbrain, pons, medulla, and spinal cord

A
  • neural progenitors of spinal cord stay next to the VZ
  • ventral aspect of neural tube –> motor neurons that send out axons out of ventral root to myotome (basal plate)
  • dorsal aspect of neural tube –> neurons that receive inputs from dorsal root ganglion with sensory info (alar plate)
124
Q

Describe the basic scheme of dorsoventral patterning of the prosencephalon, and how this relates to the adult 3D structure

A
  • dorsoventral gradient –> regional gene transcription –> differentiation
  • rostral neural tube forms DV markers to form 3 discrete zones –> dorsal cortex, lateral/medial ganglionic eminences, and basal forebrain
  • lateral surface of telencephalon vesicle folds over itself to form sylvian fissure; lateral ventricle and caudate makes a C shape
125
Q

Describe the gradients involved in neural tube formation

A
  • cerebrus by anterior visceral endoderm at rostral end
  • nodal, wnts, FGFs, and retinoic acid at caudal end promote caudal neural tube differentiation by primitive node
  • BMPs laterally and chordin/noggin/follastatin medially –> forms neural tube
126
Q

What is a myelomenigocoele?

A
  • incomplete closure of the caudal neural tube –> plaque of neural tissue contiguous with the epidermis
  • less severe version is where neural tube closes but not surrounded completely by sclerotome that makes vertebral arch –> make a dimple
127
Q

What is anencephaly?

A
  • incomplete closure of the anterior neuropore –> forebrain structures do not develop
128
Q

What is anencephaly?

A
  • incomplete closure of the anterior neuropore –> forebrain structures do not develop
129
Q

Discuss when and where neurogenesis occurs

A
  • neurogenesis starts when the neural tube starts to form
  • proliferating cells are found in regions called ventricular zones which are the layer closes to the neural tube lumen/ventricle
  • neurogenesis occurs prior to birth usually
  • in cerebellum, granule neurons as well as olfactory and hippocampal neurons are born after birth
130
Q

Describe the changes in nuclear position that occur during the cell cycle of neuronal precursors

A
  • in G1: nucleus is generally in the center, halfway between ventricle and pia
  • in S: nuclei move outward towards pia
  • in G2: return back to center
  • in M: nuclei are close to ventricular side and one process detach from external surface
131
Q

Describe methods used to study neurogenesis

A
  • label dividing cells with detectable DNA precursors
132
Q

Describe what is meant by a neuron’s birthdate and discuss whether a neuron’s birthdate influences its differentiation

A
  • a neuron’s birthdate is the time it undergoes its last round of DNA synth (S phase)
  • after M, daughter cells reattach process to external surface or can detach other process and stop dividing (post mitotic) –> differentiation starts
133
Q

Identify which brain regions are areas of secondary neurogenesis

A
  • external granule layer of cerebellum
    • initially located near rim of 4th ventricle –> migrate over purkinje cells and form a neurogenic region called external granule layer –> proliferate then exit cell cycle –> migrate into cerebellum
  • subventricular zone
    • for olfactory neurons
    • originates in VZ found in the anterior lateral wall of the lateral ventricles –> migrate to subventricular zone, just adjacent –> exit mitotic cycle –> migrate from anterior wall of lateral ventricle to more rostral location to give rise to olfactory bulb neurons
  • dentate gyrus
    • VZ –> dentate gyrus –> hippocampus
134
Q

Describe what is meant by a neuron’s birthdate and discuss whether a neuron’s birthdate influences its differentiation

A
  • a neuron’s birthdate is the time it undergoes its last round of DNA synth (S phase)
  • after M, daughter cells reattach process to external surface or can detach other process and stop dividing (post mitotic) –> differentiation starts
  • neurons that are born at the same time tend to end up toogether in the same layer –> follow similar programs of differentiation
135
Q

Draw and describe an asymmetric cell division

A

perpendicular and parallel

136
Q

Describe factors/mechanisms that determine when a cell stops dividing and begins differentiating

A
  • differing planes of cleavage when a cell in the VZ divides:
    1) perpendicular to ventricular surface: both daughter cells stay in cell cycle and lose attachment to external surface
    2) parallel to ventricular surface: one of daughter cells loses attachments and becomes post-mitotic
  • different inheritance of cytoplasmic proteins, mRNAs, and other factors depending on where in the cell they are concentrated and what type of division occurs
137
Q

For the cerebral cortex, describe where the first-born cells are found with respect to the VZ

A
  • they migrate a distance of several cell bodies at the preplate
138
Q

Define preplate and subplate with respect to neuronal migration

A
  • preplate: where the first neurons in the cortex migrate to at 9wks
  • preplate divides into marginal zone (superficial and adjacent to pia surface), cortical plate (internal layer), intermediate zone, and the subplate (between VZ and SP), and deep ventricular zone
  • IZ contains neuronal and radial glia processes
139
Q

Describe the role that radial glia play in neuronal migration

A
  • radial glia extend from ventricle to the surface

- neurons migrate into the CP using radial glia as a scaffold in a inside-out fashion

140
Q

Define and describe 3 stages of neuronal migration in the cerebral cortex

A

1) onset of migration
- involves modulation of the actin cytoskeleton
- neurons get on radial glia

2) ongoing migration
- exit VZ and migrate towards CP

3) migration stop
- once in CP, neurons get off radial glia

141
Q

Describe genes that play a role in neuronal migration and ID what class of neurons undergoes radial migration, tangential migration, chain migration

A
  • filaminA gene encodes actin-binding crosslinking protein for onset of migration
  • LIS1 and DCX are important in lissencephaly; LIS1 and DCX colocalize with microtubules and produces microtubule polymeriziation
  • reeler encodes reelin –> normal inside out pattern is inverted; reelin expressed by CR cells –> plays a role in stopping migration
  • tangential migration: GABA containing cells in the cortex; dispersed throughout tissue
  • chain migration: SVZ to lateral ventricle to olfactory bulb; neuronal precursors move as chains through rostral migratory stream
142
Q

Describe neural crest cells and the neuronal populations they give rise to

A
  • NCCs are on top of dorsal neural tube

- give rise to PNS and pigment cells and cartilage and gut, skin, and sensory ganglia

143
Q

Contrast migration of neural crest cells to radial migration in the cerebral cortex

A
  • NCCs don’t need radial glia
  • NCC’s position rostrocaudally changes its fate (NCCs atop anterior spinal cord –> enteric nervous system; posterior positions –> aorta and symp ganglia)
  • dorsal stream: flows dorsolaterally under ectoderm and lateral to myotomes –> form pigment cells
  • vental stream: flows ventromedially between dermamyotomes and notocord –> form sensory, autonomic, and enteric ganglia
144
Q

Compare and contrast “apoptosis” with “necrosis”

A

necrosis:
- occurs in response to extreme physiological changes –> causes death by loss of membrane integrity and surroundings are exposed to contents of cell
- mito and ER swell
- usually due to trauma or ischemia

apoptosis:

  • normal physiological circumstances
  • removal of cells by phagocytosis
  • surroundings aren’t exposed to contents of cell
145
Q

Describe when cell death occurs in the nervous system

A
  • damage/injury

- programmed for pattern formation, morphogenesis, etc.

146
Q

Define and describe what neurotrophins are and the roles they play in neuronal development

A
  • neurotrophins promote cell survival
  • family of related proteins: NGF, BDNF, NT3, NT4/5
  • survival factor for peripheral neurons
  • regulate neuronal survival, development, and function in CNS
  • interact with membrane receptors Trk: TrkA (NGF), TrkB (BDNF and NT4/5), and TrkC (NT3)
  • p7hNTR belongs to tumor necrosis factor receptor family
  • activation of Trk receptor –> Trk dimerization –> phos cytoplasmic signaling molecules –> recruit intracellular signaling molecules

*- neurotrophins play an early permissive role to allow cells to extend processes rather than guide them

147
Q

Provide examples of long-range and short-range axon guidance molecules and ID which are attractive or repulsive

A

long range:

  • diffusible
  • netrins (attractive)
  • semaphorins, netrins (repulsive)

short range:

  • bound to cell membranes or ECMs and require direct cell contact
  • cadherins, CAMs, collagen, laminin, fibronectin, proteoglycans (attractive)
  • semaphorins, ephrins, tenascin (repulsive)
148
Q

ID factors that influence the ability of axons to regenerate

A

1) the ability of axons to grow:
- can grow long distances (many centimeters)

2) presence of molecules that promote growth:
- glial environment
- schwann cells can make NGF or other neurotrophins or FGF

3) the presence of molecules and receptors that inhibit growth:
- CNS myelin expresses a molecule that prevents axonal regeneration in adults
-

149
Q

Describe when myelination occurs

A
  • begins during embryonic stages and is first present in periphery
  • in CNS, first seen in spinal cord near end of first trimester
  • by the end of third trimester, myelination is seen in brain
  • myelination of several cortical tracts doesn’t happen until birth
  • after birth, more caudal regions of CS tract become myelinated
150
Q

Describe normal postnatal changes in brain morphology and how Autism Spectrum Disorder and Down’s syndrome affect these normal developmental changes in neuronal morphology

A
  • at birth, density of neural connections is low but more happen over time

ASD:

  • inc in brain size, especially white matter
  • cell bodies are smaller and dendrites branch less

Down’s

  • dendritic spines are thin and short
  • reflects abnormal pruning or synapse maturation
151
Q

Describe two ways in which the function of GABA receptors is developmentally regulated

A
  • in adult, ECl is near or negative to the resting membrane potential
  • during developmental stages, intracellular levels of Cl are elevated –> more depolarized value for ECl –> activating GABA receptors leads to depol and excitation
152
Q

Define synapse elimination and discuss when and where it occurs

A
  • the process where you start with a single muscle fiber receiving input from several motor neurons to finally each muscle fiber being innervated by one and only one neuron
  • this process starts soon after birth
  • correlated firing of pre and post synaptic cells favor selective synapse stabilization
153
Q

Define synapse elimination and discuss when and where it occurs

A
  • the process where you start with a single muscle fiber receiving input from several motor neurons to finally each muscle fiber being innervated by one and only one neuron
  • this process starts soon after birth
  • correlated firing of pre and post synaptic cells favor selective synapse stabilization
154
Q

Describe Neural Tube Defects and when during embryogenesis/development it occurs

A
  • arise from failure of the neuroectoderm to form a complete tube during primary neurulation
  • or disordered diff of caudal cell –> conus med and filum term during secondary neurulation
  • cranioraschisis totalis: complete failure of primary neurualtion
  • anencephaly: failure of rostral neuropore to close –> forebrain fails to separate
  • encephalocele: protrusion of leptomeninges and brain from skull; epidermal covering over closing defect
  • myelomeningocele: post neuropore closure failure; CSF leak
  • meningocele: skin covered CSF filled mass cont with CSF in spinal cord
  • lipomyelocele: lipoma from subcut tissue to dorsal aspect of cord and tethering the cord inferiorly; premature separation of cut ectoderm during neurulation –> mesenchyme enters unclosed neural tube and turn into fat
  • dorsal dermal sinus tract: ectoderm lined tracts that transgress the dura and allow communication between skin and CSF
  • spina bifida: bony laminary arch doesn’t close
155
Q

Describe holoprosencephaly and when during embryogenesis/development it occurs

A
  • single ventricle in early embryonic forebrain fails to form into two lateral ventricles and one third ventricle
  • takes placed during fifth week of fetal life

1) alobar HPE: single forebrain with single ventricle
2) semilobar holoprosencephaly: partial cleavage of hemispheres fused at frontal
3) lobal holoprosencephaly: separated anteriorly and posteriorly with some fusion

  • ## facial deformities
156
Q

Describe association between Chiari I and syringomyelia

A
  • cerebellar tonsils that are elongated and pushed down through foramen magnum –> blocks flow of CSF exiting central canal
  • CSF filled cyst forms and breaks out of central canal and dissect cord –> syringomyelia
157
Q

Describe association between Chiari II and myelomeningocoele

A
  • elongation of cerebellar vermis –> pushed down through foramen magnum and blocks CSF flow
  • breaking of midbrain tectal plate and kink in medulla
  • confluence of sinuses
  • ## thoraco-lumba MMC
158
Q

Discuss the principal causes and consequences of stroke in the perinatal period

A
  • caused by vascular malformations, congenital heart malformations, genetic clotting problems, sickle cell, heriditary polycythemias, neurocutaneous syndromes and rare primary vascular diseases
  • 55% ischemice, 45% hemorrhagic
  • unusual position of infant leading to distortion of infants neck –> stretching of carotid arteries –> vascu insuff during birth –> infarcts –> mushroom shaped gyri
  • lead to cerebral palsy
  • ## hemorrhage into germinal matrix in preterm infants
159
Q

What is tethering of the spinal cord?

A
  • prevention of ascension of conus med over time
  • compromised blood supply and resultant spinal cord dysfunction
  • leads to pain, UMN signs, urinary incontinence
160
Q

What is dandy-walker malformation?

A

a) partial or complete absence of formation of the cerebellar vermis
b) cystic dilation of 4th ventricle
c) upward displacement of tentorium
d) hydrocephalus

161
Q

What is dandy-walker malformation?

A

a) partial or complete absence of formation of the cerebellar vermis
b) cystic dilation of 4th ventricle
c) upward displacement of tentorium
d) hydrocephalus

162
Q

Recognize the clinical features of ALS, CMT, DN, MG, and DMD

A

ALS:

  • progressive weakness due to degen of brainstem and LMNs and UMNs (pathological reflexes)
  • affects lateral CS tract
  • asymmetric limb weakness with fasciculations, foot drop, hand deformity

Charcot Marie Tooth:

  • AD inheritance
  • either slow nerve + hypertrophic demyelination or normal nerve + axonal degen
  • distal weakness and sensory loss in first 20yrs of life; delayed walking; adult onset

Myasthenia Gravis:

  • weakness and fatigue in
  • ptosis
  • opthalmoparesis

DMD:

  • X-linked
  • waddle, gower’s
  • large calves
163
Q

Recognize the pathologic changes of ALS, CMT, MG, and DMD

A

ALS:

  • unpredictable: weight loss, muscle loss, swallowing probs, diaphragm weakness, 3-4yr survival rate
  • treat symptoms and cramps, spasticity, saliva with riluzole

CMT:

  • delayed walking
  • contractures, deformities
  • treat by inc QOL
164
Q

Discuss the common genetic defects in CMT and DMD

A
  • CMT1A: a duplication of gene containing peripheral myeling protein gene PMP22; deletion of PMP22 leads to HNPP
165
Q

Describe the immune-pathogenesis and treatment of MG

A
  • AI Abs against ACh receptors postsynaptic
  • thymoma associated
  • treat with plasmapharesis and steroids

neuro (4 decks)

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