Neurotransmission

Question 1

CNS inputs

Answer 1

All connections between peripheral afferents and CNS neurons are excitatory
requires balance by CNS inhibition
processing often involves removing unwanted inputs

Question 2

Presynaptic inhibition

Answer 2

more selective than post-synaptic
- lower effectiveness of one or a few inputs to an euron
- does not affect other inputs or postsynaptic membrane potential
major pathway in spinal cord

GABA is the major NT
GABAa receptors: Chloride conductance, shunting of AP
GABAb receptors: long -acting; G-protein coupled modulation of K and Ca channels

Axoaxonic, and dendroaxonic interaction

Question 3

Recurrent inhibition

Answer 3

Autoregulation of motor neuron firing rates
Modulation of motor output by its own activation
Glycine dominant NT, but also GABA
Convergent synaptic input from descending pathways
Renshaw cells involved

Question 4

Renshaw cell

Answer 4

recurrent inhibition of motor neurons
spinal interneurons
Excited by collaterals from motor neurons, and then inhibit those same motor neurons –> negative feedback
Regulates motor neuron excitability and stabilizes firing rates

Question 5

Golgi tendon organ

Answer 5

GTO stretch (contraction of muscle) --> afferent axon compressed by collagen fibers --> rate of firing increases
Disynaptic GTO inhibition and the Ib inhibitory interneuron = inverse myotactic reflex, "clasp knife reflex"
Ib feedback from GTO inhibits contraction of agonist, and facilitates antagonist

Question 6

Pyramidal/CST

Answer 6

~ 1 million fibers, mostly myelinated
lateral fibers decussate at midbrain (not all cross)
projects to alpha and gamma motor neurons, interneurons
Monosynaptic connections
Also indirect pathways (rubrospinal, reticulospinal)

Question 7

Reticulospinal tract

Answer 7

Innervates LMN, affected by supraspinal projections
Activity controls posture and strength of reflexes
Interruption in pathway leads to deficits

Question 8

Interruption of descending input

Answer 8

“releases” spinal interneurons, of which many are inhibitory
Unrestricted flow of excitation reaches motor neurons
- hyperreflexia
- can also affect the sign of reflexes (e.g. Babinski, Bing)

Question 9

LMN disorder characteristics

Answer 9

flaccid weakness or paralysis
decreased or absent monosynaptic reflex
muscle denervation, atrophy
affects single muscles or small groupw innervated by common nerve
cutaneous reflexes normal

Question 10

UMN disorder characteristics

Answer 10

spastic weakness (increased velocity sensitivity)
exaggerated monosynaptic reflex
clonus (5 Hz)
no signs of denervation, atrophy
large groups affected, organized by halves or quadrants of the body
reversed (Babinski) or absent cutaneous reflexes

Question 11

Spasticity

Answer 11

Hypertonia
Hyperreflexia
more pronounced in anti-gravity muscles: flexors in the arm, extensors in leg

Question 12

UMN lesion treatment

Answer 12

Diazepam (Valium)
- antispastic action by increasing frequency of GABAa receptor channel openings, enhancing postsynaptic inhibition in spinal cord

Baclofen: reduces spasticity by activating presynaptic GABAb receptors, inhibiting glutamate release from afferent fibers

Question 13

Excitotoxicity

Answer 13

Ischemia –> glutamate release –> activation of glutamate receptors –> Na influx –> activation of VaC channels –> influx of Ca –> neuronal injury

Question 14

Neuronal body vacuolation

Answer 14

cytotoxic edema (failure of pumps, water influx)
Prion diseases (spongiform encephalopathy)

Question 15

Neuromelanin

Answer 15

normal
byproduct of catecholamine synthesis
in neurons of substantia nigra and locus cereleus
differs from skin melanin

Question 16

Lipofuscin

Answer 16

pigment of aging

in many neurons

Question 17

Axonal reaction/central chromatolysis

Answer 17

Response of nerve cell body to axonal transection
Swollen cell body with displaced nucleus, dispersed Nissl substance
increased mRNA synthesis –> increased protein synthesis

Question 18

Wallerian degeneration

Answer 18

degeneration of distal fragment of axon after axonal transection

Question 19

Axonal retraction balls

Answer 19

damming up of organelles conveyed by axonal transport to proximal stump of axonal transection site

Question 20

Axonal spheroids

Answer 20

seen in neuroaxonal dystrophies
certain locations in aging
light microscopically similar to, but ultrastructurally different from, axonal retraction balls

Question 21

Dendritic reactions

Answer 21

abnormalities in number, shape, and size of dendritic spines in mental retardation/epilepsy

Question 22

Astrocyte function

Answer 22

"scar" cell of CNS
support and structure
syncytium throughout CNS
Energy from glycolysis
Glutamate and GAPA uptake
pH, osmolarity regulation
spatial buffering of K+
glutamine for glutamate synthesis
gray matter: protoplasmic
White matter: fibrous

Question 23

Gliosis changes

Answer 23

early: hyperplasia, hypertrophy, upregulation of GFAP
Late: fibrillary gliosis

Question 24

Astrocytic swelling

Answer 24

Rosenthal fibers

• linear/corkscrew hyaline inclusions
• seen in long-standing gliosis

Question 25

Astrocytic inclusions

Answer 25

Corpora amylacea - round inclusions of glycoprotein - in astrocytic foot processes - particularly around blood vessels, or near surfaces of CNS

Question 26

Ependyma reactions

Answer 26

lining of ventricles destruction of ependymal cells probably not replaced with other ependymal cells Subventricular glial nodule (Granular ependymitis): non-specific reaction of subventricular astrocytes to ependymal injury/loss

Question 27

Microglial reactions

Answer 27

CNS cells originally derived from bone marrow Phagocytic function Antigen presenting Activated in response to CNS injury in absence of parenchymal destruction Turns into macrophages in response to CNS injury with parenchymal destruction

Question 28

Immune response in the CNS

Answer 28

Class II MHC-controlled Class I cMHC controlled Often don't see T and B cells due to immunological priviledge

Question 29

Class II MHC-controlled immune response

Answer 29

Normally minimal constitutive Class II MHC in white matter microglia CD4 TCR recognizes Ag in the context of Class II MHC on the APC Need other co-stimulatory molecules and receptors T-cell + APC --> proinflammatory cytokine profile --> immune response to antigen initiated OR immunomodulatory cytokine profile --> immune response to antigen suppressed

Question 30

Class I MHC-controlled immune response

Answer 30

Interaction between cytotoxic T-cell and target/APC --> lysis/apoptosis of target cell Normally constitutive class I MHC on endothelial cells and probably some glia and perivascular cells in the CNS CD8 TCR recognizes antigen (peptide) in context of Class I MHC on target cell no intermediary cell to carry out target destruction

Question 31

CNS immunological privilege

Answer 31

Activated T-cells breach BBB Unactivated T-cells do not traffic through CNS Immune response in CNS will only result from a trafficking T-cell if: - T cell receptor recognizes a specific CNS antigen - antigen is presented in context of MHC to T-cell CNS normally has very FEW APCs

Question 32

Multiple sclerosis pathophys

Answer 32

autoimmune disease of CNS myelin sheath | Gliosis in demyelinated plaques of MS

Question 33

Inflammation in MS

Answer 33

``` Lymphocytes monocytes macrophages perivascular inflammation initiation and extension of actively demyelinating plaque --> CD4 T-cells in perivascular spaces ```

Question 34

Antigen presentation in MS

Answer 34

Antigen first presented to trafficking activated T-cells by perivascular microglia (Class II MHC) Subsequent antigen presentation to T-cells by macrophages in plaque

Question 35

Demyelination in MS

Answer 35

macrophages - removes myelin lamellae from sheath - internalized myelin degraded to neutral lipid in macrophage lysosome Axons are relatively intact

Question 36

Remyelination in MS

Answer 36

Increased #s of oligodendrocytes and remyelination seen in actively demyelinating MS plaques Remyelinated myelin also undergoes macrophage attack

Question 37

Chronic silent MS plaque

Answer 37

little inflammation remains ? due to suppressor cells or immunomodulatory cytokines down-regulating immune response Plasma cells persist and produce IgG Lipid-laden macrophages make their way to perivenular spaces, and then to systemic circulation Numerous demyelinated axons and fibrillary gliosis some axonal loss