B2W3 Flashcards
Effects of demyelination
decreasing velocity of AP (due to it leaking out of channels and taking longer to travel), total conduction blocks, ectopic generation of APs, increases in chemosensitivity, and cross talk (leaking AP then propoxate other neurons)
Neuronal Firing Patterns and their adaptation patterns (in inhibitory, small pyramidal and large pyramidal)
-Inhibitory interneurons (limited adaptability)
-small pyramidal cells (some degree of adaptation)
-large pyramidal cells (large degree of adaptation, with some bursts of APs
Eserine effect on cell
inhibits AChE, allowing ACh to stay in the cleft longer
Mg level increase in cell
blocking more Ca channels, leading to a decrease in vesicular fusion
Increasing SuccinylCh in cell
flaccid paralysis, leading to an electrically inexcitable cell
Curare effect on cell
inhibits AChR - causing EPP to decrease (sometimes safety factors can save the cell if at a low level)
How to rescue curare cells?
if curare inhibits AChR, then we can inhibit AChE to allow for more ACh in the synaptic cleft
Length constant
Length constant = radius * resistance of membrane / 2* internal neuron resistance (length constant is trying to measure how far a AP will travel down an axon
Attenuation
accounts for the reduction of force and how likely a EPSP will decrease over time
Attenuation v Length constant
longer the length constant, less attenuation (less resistance and less decrease of an EPSP, giving rise to a longer travel)
_____ resistance causes leakage through neuron membranes
High
Spatial summation
multiple synapses leading to a rapid influx of EPSPs onto one group or synapse
Temporal summation
rapid influx of stimulation from the same synapse
Which part of the neuron have the highest amount of Na channels?
The axon hillock and the nodes of ranvier have the highest levels
Lowest threshold in an axon
initial segment
Dendrites propogating an AP?
Dendrites do not often propogate their own, but in the purkinjee fibers of the cerebellum there is a high density of Ca channels which can generate Na movement and AP generation
Axospinous synapse
on the spines of a dendrite - has fast EPSPs
Shaft synapse
on the shaft of the dendrites - has fast IPSP
Axo somatic synapses
synapse onto the soma of a neuron, have fast IPSP
Axoaxonic synapses
synapse onto an axon - usually modulatory affects
4 types of neuronal firing patterns
Repetitive
Adaptation (inhibition of K channels)
Thalamic Relay (using low voltage Ca channels)
Spontaneous
Divergence v convergence
divergence: one neuron, one neurotransmitter, many targets
convergence: many neurons, many neurotransmitters, one target
Recycling of ACh in synapse
Biosynthesis in presynaptic terminal, packaging, release, receptor activation, removal from synapse
PNS Cranial Nerves
III, VII, IX, X
III
oculomotor nerve
VII
facial nerve
IX
glossopharyngeal nerve
X
vagus nerve
CNS control of PNS (which brain parts)
hypothalamus, nucleus tractus solitarius, nuclei of the medulla
Enteric NS (general properties)
controls motility of the GI tract, and has both parts of the parasympathetic (preganglionic), and sympathetic (post ganglionic)
Sensory Nerves entrance into the spinal chord
doral afferent root via the dorsal root ganglion
Somatic nerve exit out of the spinal chord
ventral efferent root and toward peripheral nerve to target
Paravertebral pathway traveling out of the spinal chord
this is SYMPAthetic: preganglions leave the thoraco-lumbar region of the ventral root and enter the white ramus (myelinated), then synapses in the paravertebral ganglia. Then the postganglionic nerve passes through the grey ramus (unmyelinated), through the peripheral nerve and toward its target
Prevertebral pathway traveling out of spinal chord
this is SYMPAthetic pathway: preganglions travel out of the ventral root, through the white ramus and into the prevertebral region. Then it synapses and postganglion travels to target
Neurotransmitter for Somatic NS
ACh
Neurotransmitters for PNS
ACh on both pre and postganglion
Neurotransmitter for SympaNS
ACh on pre, norepi on post, epi for post adrenal medulla
Receptor types for preganglions
Nicotinic
Receptor types of postganglions
PNS: muscarinic (cholinergic) SNS: muscarinic (adrenergic)
Catecholamines
NE and EPI
Preganglionic innervation location for PNS and SNS
BOTH ARE IN THE CNS
PNS: cranio-sacral with innervation from X
SNS: thoraco-lumbar
Post ganglionic locations PNS v SNS
PNS: near target cells
SNS: located in the paravertebral, prevertebral and adrenal medulla
Fiber length of pre and post ganglions for PNS v CNS
PNS: pre (long) post (short)
SNS: pre (short) post (long)
Similarities between SNS and PNS
2 neuron chains, preganglions in CNS and myelinated, postganglion in PNS and unmyelinated
SNS v PNS physiological responses
SNS: increase HR, bronchioles dilate, pupils dilate, decrease GI motility, contracted sphincters, relaxed bladder, ejaculation
PNS: decrease HR, bronchioles constrict, pupils constrict, increase GI, contracted bladder, relaxed sphincters, erection
Point and shoot
P = parasympathetic = erection
S = sympathetic = ejaculation
QIQ QUISS
QIQ = PNS (M1, M2, M3)
QUISS = SNS (a1, a2, b1, b2)
Alpha and beta …. which is dilation?
a1, b1 = vasoconstriction
a2, b2 = vasodilation
Alpha 1 adrenergic receptors
vascular smooth muscles, increases intracellulas Ca to contract blood vessels and induce vasoconstriction
Beta 1 adrenergic receptors
heart, stimulates Galpha S for increase in cAMP and increase HR through vasoconstriction
Beta 2 adrenergic receptors
located throughout the body, stimulates Galpha S to cause dilation in SNS responses (pupil dilation, bronchiole dilation)
Sympathetic innervation of smooth muscle (contraction)
3 ways:
ATP (P2X and activation of voltage gated Ca channels)(fastest)
NE (synaptic release from A1 receptors, leading to Gq rise in intracellular Ca) (middle response)
Neuropeptide Y (synaptic release, binding to Y1 and leading to increase in intracellular Ca)(slowest)
Parasympathetic innervation of smooth muscle (relaxation)
3 ways: (ACh and NO are faster)
ACh (synaptic release of ACh leading to the binding to GalphaQ on endothelial cells. PLC activation and IP3 increases intracellular Ca. Rise in Ca leads to activation of eNOS which creates NO which can diffuse out of endothelial cell and into smooth muscle cell for GC activation and rise in intracellular cGMP)
NO (nNOS conversion of L-arginine to NO to allow for diffusion across membrane into smooth muscle cells where it binds to Guanyly cyclase and the hydrolyzes GTP to cGMP)(rise in intracellular cGMP leads to relaxation of a cell)
VIP (colocalizes with ACh to be released into vesicle, leading to binding of VIP receptor and decrease in Ca)
Horner’s Syndrome (mechanism)
damage to paravertebral ganglia in the sympathetic NS leading to loss of sympathetic innervation on one side of the face
Horner’s Syndrome (clinical presentation)
ptosis (eye dropping), miosis (constriction of the pupil), anhidrosis (lack of sweating)
Local circuits in the CNS
they are within a certain brain region
have 3 parts (input, interneuron, output)
interneurons can either inhibit or excite
alpha motor neurons carry signals
generation of motor outputs is the result
Neuronal circuits that produce rhythmic motor outputs and spinal reflexes are highly dependent on ____________
inhibitory interneurons
Sensory (afferent) muscle fibers:
1A: mainly big muscle fibers, reporting changes in length (is muscle moving)
2: mainly chain muscle fibers (report static muscle length) (how contracted am i)
2B: Golgi tendon organ senses in tendons
Motor (efferent) muscle neurons
Alpha: force generating , extrafusal fibers
Gamma: intrafusal fibers, innervate fibers of muscle spindles and maintains muscle length
3 types of inhibition
Feedback, lateral, and feed forward
Alpha motor neuron
extrafusal fibers
gamma motor neuron
intrafusal fibers
Myostatic (knee jerk reflex)
Monosynaptic -
hammer hits knee - stimulates extensor (quad) (contracts), inhibition of flexor (hamstring) relaxes causing knee to kick up
1A sensory monosynaptic neuron carries message to the spine with direct synapse onto alpha motor neuron of quad
1A sensory neuron synapses onto inhibitory interneuron that inhibits the alpha motor neuron of the hamstring causing relaxation
reciprocal innervation
one activation leads to one inhibition
Golgi Tendon Reflex
contraction of one muscle (quad) leads to an increase in tension causing 2B neurons which sense the shortening of the muscle. Polysynaptic pathway inhibiting the extensor muscle (quad) leading to the contraction and activation of the flexor muscle (hamstring) to aid in further shortening of the muscle
Flexion Withdrawal Reflex
nociceptors notice pain.
extensor muscle of the hurt leg will relax with activation of the flexor (hamstring) leads to foot picking up
extensor muscle on the solid leg will contract with flexor relaxation leading to solidification of balance
Central Pattern Generators
based on inhibitory neurons and reciprocal inhibition meaning flexors and extensors are never activated at the same time (CAT VIDEO WALKING)
Visual Projection of the (R) eye
(R) direction is seen in the (L) lateral eye leading to the (L) LGN leading to the (L) primary cortex
Visual projection in the (L) eye
(L) direction is seen in the (R) lateral eye leading to the (R) LGN to the (R) primary visual cortex
Eye site (general)
eye, optic nerve, optic chiasm, optic tract, LGN, visual cortex
Ocular integration
monocular eyesite until the approaching the LGN and onto the striate cortex (6 layers) of the visual cortex which processes and creates and image
Which column is the Striate cortex found
IV
dominance columns v blobs and where they are found
dominance columns - integration of information
blobs - color and motion
dominance columns = IV
blobs - II and III
Low Frequency
longer wavelengths, being able to tell lower frequency through interaural delay
Relate delay lines to coincidence factors
delay lines - axons bringing potentials to the MSO from each cochlear nucleus
coincidence factors - when axon potentials arrive at the MSO at the same time from L and R this leads to AP generation and hearing of a sound
High frequency sound
interaural intensity (ear facing sound will hear it louder) shorter wavelengths to not permit time for delay
Pathophysiology for MS (generally what is MS)
chronic inflammation leading to a loss of myelination leading to an overall decrease in saltory conduction
Risk Factors for MS
women, genetic factors (mutations in HLA)(+ EBV), smoking, low vitamin D, obesity, diet, gut microbiome composition
Clinical Symptoms
Visual symptoms (diplopia)
Ataxia (clumsiness/loss of balance)
Paresthesia (numbness in extremities)
Hyperesthesia (increasing sensitivities)
Vertigo (balance issues)
Immunology of MS
T cell:
-T(reg) dysregulation leading to the overexpression of T1 and T17 which are proinflammatory T cells leading to an increase in inflammation of the CNS
B cells:
-CD20+ B cell density has been seen in demyelinating lesions of MS, also ectopic lymphoid follicle-like aggregates are seen which are also consistent with primary progressive MS
-premature maturation leading to B cells being able to create antibodies that attack myelin in an inflamed CNS
The Main T cells which are involved in MS
T(reg), T1, T17
Pathophysiology of MS (main hallmarks physiologically)
alterations in the BBB, neuronal loss, myelin and axonal degeneration, and gliosis
White v Grey matter in MS
White: (myelinated) - inflammation, demyelination, neurodegeneration
Grey: (unmyelinated) - atrophy leading to clinical disability, most likely linked with the progression of the disease
Two Types of MS
- Relapse Remitting MS
- Primary Progressive
Diagnosis of RRMS v PPMS
-Clinical Diagnosis of MS can be satisfied with clinical symptoms, but for RRMS there needs to be DIT and DIS
DIS v DIT (definition)
DIS: dissemination in space - there is proof to show that there were different locations of lesions in the CNS
DIT: dissemination in time - there was different times when lesions occurred in the CNS
Criteria Q: 2 or more attacks, and 2 or more lesions (MS)
DIS and DIT met
Criteria: 2 or more attacks, 1 lesion with history of attack with lesion in different location
DIS and DIT met
Criteria: 2 or more attacks, 1 lesion
DIT met, DIS must be met by seeing a different location of attack, or 1 or more lesions in the periventricular, cortical, juxtacortical and intratentorial, spinal chord
Diagnostic Techniques
- obtained through a lumbar puncture to satisfy DIT
- Clinical Evaluation (attacks)
- MRI (enhancing and non enhancing lesions)
Diagnosis for PPMS
1 year of progression of symptoms (DIT)
DIS satisfaction through new lesions on MRI or in oligoclonal bands
MRI Enhancing Lesions v Non-Enhancing Lesions of MS
Enhancing: Gadolinium enhancing lesion (Gd+ lesions) (BRIGHT)(ACUTE BBB DAMAGE)
Non-Enhanding: T1 (black holes, damage) and T2 (chronic lesions showing progression of disease) (DARK)(LOSS OF MYELIN AND ATROPHY)
Treatment Goal for MS (3 things to reduce)
- # of lesions
- # of attacks
- progression of disease
Treatment for RRMS
- injectables
- oral medications
- infusions
*for acute attack, prednisone and steroids can be used to aid in symptoms
Treatment of PPMS
Ocrelizumab - depletes B cells (mature and immature)
MS v NMO v MOG (target differences)
MS - myelin
NMO - astrocytes
MOG - oligodendrocytes
MS v NMO v MOG (names)
MS - multiple sclerosis
NMO - neuromyelitis optica
MOG - myelin oligodendrocyte glycoprotein antibody disease
MS v NMO v MOG (optic Nerve MRI difference)
MS- unliteral differences - middle of optic nerve
NMO - bilateral differences with posterior optic nerve
MOG - bilateral differences with anterior optic nerve
