Term
| How is a resting potential maintained across neuronal membranes? |
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Definition
-70mV compared to a standard of 0 on the outside of the cell
- Na-K pump keeps intracellular Sodium low and Potassium high
- Forces of passive diffusion and electrostatic force counteract each other. |
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Term
| How is a reversal potential calculated and what does it mean? |
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Definition
The reversal potential tells us the voltage at which chemical/electrical equilibrium for a specific ion species.
Nernst equation allows us to calculate RP just by knowing the concentration of ions on the inside and outside of the cell.
Goldman equation is applied when there are multiple ionic species (reduces to Nernst if single ion is present). |
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Term
| How are action potentials generated? |
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Definition
"All or None" and propagate without diminishing.
1) At rest, membrane potential is dominated by passive K+ channels
2) Voltage gated sodium channels open if membrane is depolarized (1ms)
3) As membrane potential moves towards reversal potential of sodium, membrane becomes depolarized (rising phase).
4) Slower, voltage-kated potassium channels open and sodium channels begin to close. Potassium rushes out and membrane potential decreases (falling phase).
5) Potassium channels stay open long enough for membrane potential to "over-shoot" resting potential. |
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Term
| Why do action potential signals not degrade over the course of the axon? |
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Definition
"Adding amplifiers along a cable to boost signal"
1) Passive ion flow over short distances
2) Ability of passive ionic fluctuations to activate voltage-gated sodium channels. |
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Term
| How is conduction velocity regulated during membrane depolarization? |
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Definition
1) Speed of local depolarization (membrane time constant)
- smaller time constant means membrane can charge faster and conduction speed is increased.
2) How far ahead the current can spread (length constant)
- larger length constant means increased conduction velocity
** both depend on amount of curent generated and "leakiness" of aoxn" |
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Term
| How does conduction of action potentials occur in myelinated axons? |
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Definition
Saltatory conduction jumping between nodes of ranvier (containing Na channels for AP regeneration)
- Remember, myelination reduces membrane capacitance, to reduce the amount of local current required to depolarize neurons to their firing threshold.
**Metabolically favorable because less energy is spent to restore ionic concentration gradients. |
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Term
| What are the major types of Glial cells in the CNS and their basic functions? |
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Definition
Physical protection and homeostasis
1) Astrocytes (Protoplasmic/gray and Fibrous/white) supply nutrients and oxygen to neurons, modulate neurotransmission, modulate inflammation and repair CNS after trauma.
2) Microglia are macrophages of brain
3) Oligodendroglia myelinate neuronal axons (1 per neuron) |
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Term
| You section a brain taken from a patient who had MS and stain it with GFAP. What do you see? |
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Definition
Glial Fibrillary Acid Protein (GFAP)
-Protoplasmic (gray matter with fine branches in uniform globoid distribution) and Fibrous (white matter with long, fiber-type processes) Astrocytes. |
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Term
| What is the primary mechanisms of astrocyte activation as well as astrocyte-astrocyte and astrocyte-neuron communication? |
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Definition
Astrocyte Excitability
- intracellular calcium waves are propagated along the astrocyte syncytium, which is a network of gap junctions forms between their peripheral domains. |
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Term
| What type of cells give rise to Glioblastoma multiforme tumors in the CNS? |
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Definition
Germinal Zone Astrocytes (neural stem cells).
These GFAP-expressing cells arise from radial glial cells (RGCs). |
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Term
| Explain the developmental basis for glial cell differentiation. |
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Definition
1) Radial Glial Cells (GFAP-expressing) arise from neuroepithelial cells in neural tube and serve as progenitor cells and scaffolding for cortical neuron migration.
2) RGCs give rise to
- parenchymal astrocytes
- oligodendrocytes
- ependymal cells (blood brain barrier)
- GFAP-expressing germinal zone astrocytes. |
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Term
| What are the 6 major functions of Astrocytes? |
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Definition
BEST BF
1) BBB
2) Energy/Metabolism
3) Synaptic Development/Function
4) Tissue Repair
5) Blood Flow
6) Fluid balance/edema |
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Term
| How do astrocytes influence synaptic development and function? |
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Definition
1) Produce guidance cues for neuroblast migration
2) Produce molecules for synapse formation (thrombospondin)
3) Synapse pruning through complement C1q induction at synapses (tag for microglia targeting).
4) Potassium sequestration (many K channels) to prevent hyperactivity of neurons and neurotransmitter removal.
5) Gliotransmission in response to calcium signaling or neuronal activity (Tripartite synapse) |
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Term
| How do astrocytes influence Energy and metabolism? |
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Definition
Regulated by glutamate and neuronal activity
1) Take up glucose from blood vessels and produce energy metabolites and pass them to neurons through gap junctions.
2) Glycogen storage in CNS which can be broken into lactate and transferred to neurons (sustain neural activity in hypoglycemic states or periods of high activity) |
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Term
| How do astrocytes influence BBB function? |
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Definition
-Astrocyte end-feet envelope capillary endothelium , BUT there is a 20nm gap between adjacent end feet (so actual barrier is endothelial tight junctions)
- Determines function, morphology (tightness) and protein expression in BBB, as well as possibly repair. |
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Term
| How do astrocytes regulate blood flow in the CNS? |
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Definition
| Autoregulation of blood flow through production of prostaglandins, NO and AA, resulting in neurovascular coupling to increase blood flow to regions in which neurons are active |
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Term
| How do astrocytes influence Fluid balance/edema? |
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Definition
1) Aquaporin 4 for water balance
2) VEGF and NO to influence permeability |
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Term
| How do astrocytes influence Tissue Repair? |
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Definition
Astrocytosis/gliosis involving hypertrophy, proliferation and scar formation (glia are not post mitotic).
Neuroprotective- neurotransmitter uptake, barrier protection against infection, BBB repair, stabilizing ECF and ion balance, reducing vasogenic edema after trauma/stroke.
1) Mild gliosis involves variable up-regulattion of GFAP, hypertophy of cell body and processes without loss, no proliferation and little reorganization of tissue architecture.
2) Moderate/severe gliosis involves pronounce up-regulation of GFAP, hypertrophy, proliferation and persistent reorganization of tissue architecture leading to GLIAL SCARS. |
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Term
| What is the developmental origin of microglia? |
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Definition
** eat up the debris during neurogenesis!!**
- Early microglial drive from yolk sac monocytes that seed the CNS in mid-gestation in order to phagocytose cell debris generated by apoptosis.
- Monocytes from bone marrow continue to to populate CNS throughout development
- Early microglia have "ameobid" morphology that allows movement through neural tissue |
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Term
| What is the difference between Resting, ramified microglia and "activated" microglia? |
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Definition
1) Ameboid microglia revert to "resting" state with small cell bodies, rod-shaped nuclei and long branching processes. These cells do not phagocytose ells, but serve IMMUNOSURVEILANCE.
2) When immunologic/chemical stimulus activate resting microglia, they uptake MHC class I/II proteins and assume antigen-presentation capability.
- Retraction and thickening of processes occurs, and many develop the ability to phagocytose (glitter or foam cells)
"Activated" microglia recruit pro-inflammatory signals, which permits lymphocyte and macrophage influx from bloodstream. T cells cross BBB and directly bind microglia to recognize presented antigens
**also activate astrocytes** |
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Term
| How do microglia contribute to CNS pathology? |
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Definition
1) Analogous to chronic astrocytosis, chronic activation can lead to inflammatory tissue damage (non-specificc)
2) HIV-activated microglia are main source of AIDS dementia
3) In AD, neurons produce b-amyloid peptides which activate microglia, causing injury to degenerating neurons. |
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