Cell Biology of Neurons and Glia Flashcards

1
Q

What determines passive membrane properties of the neuron?

A

Conductance of non-voltage gated ion channels, membrane capacitance, and resistivity of the cytoplasm.

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2
Q

What determines the active membrane properties of the neuron?

A

All of the passive determinants as well as concentration and distribution of ion channels controlled by voltage, neurotransmitter or ligand binding, or a second messenger system.

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3
Q

What are the four structural compartments of the neuron?

A

Dendrites, cell body, axons, synaptic terminals

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4
Q

What are the three forms of axoplasmic transport and what purpose do they serve?

A

Fast anterograde transport: transports organelles and vesicles towards the synapse and is mediated by kinesin Slow anterograde transport: transports cytoskeletal proteins by bulk flow Fast retrograde transport: transports trophic factors, signaling molecules, endosomes, and lysosomes back to the cell body via dynein

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5
Q

What can disrupt axoplasmic transport? What symptoms does this cause? What foreign agents can also be transported this way?

A

Fast axonal transport is compromised by a lack of oxygen or microtuble destablizing drugs (i.e., colchicine) which can lead to neuropathy. Viruses can also infect the neuron and be transported to and from the cell body by these mechanisms.

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6
Q

What type of current flow (active or passive) is required for action potential conduction?

A

Both–voltage gated ion channels are opened in response to passive depolarizing current flow down the axon.

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7
Q

What two features of action potential firing are important for signaling?

A

Number of action potentials and the time interval between them (rate)

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8
Q

What are the roles of glia in the CNS and PNS?

A

Regulation of cell migration and axon guidance Formation of the blood brain barrier (astrocytes) Trophic and insulating functions (oligodendrocytes myelinate axons in the CNS, Schwann cells myelinate axons in the PNS) Modulation of synaptic function Mediate response to injury (microglia serve phagocytic and inflammatory functions) Maintain extracellular environment (astrocytes)

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9
Q

What is the difference between myelination in the CNS and PNS?

A

Oligodendrocytes myelinate axons in the CNS and have many processes that wrap around segments of different axons. Schwann cells line up along the axon and wrap around it entirely, therefore a single axon is myelinated by many Schwann cells.

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10
Q

What is saltatory conduction?

A

Conduction along a myelinated axon that jumps from node to node. Only the nodes contain ion channels that regenerate action potentials and the space between nodes has very low capacitance

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11
Q

What two properties of the axon impact the speed of transmission?

A

Myelination and diameter–increasing both increases speed

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12
Q

What is Charcot-Marie-Tooth disease? What mutation causes it?

A

Charcot-Marie-Tooth disease is a peripheral demyelination disorder caused by autosomal dominant mutations in peripheral myelin protein 22 (PMP22). It is characterized by progressive loss of muscle tissue and touch sensation.

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13
Q

Describe synaptic transmission of PNS synapses. How many synapses are needed to affect the postsynaptic cell? What neurotransmitters are involved? How are they eliminated?

A

The main synapse in the PNS is the neuromuscular junction. When an action potential reaches the terminal, voltage gated calcium channels are opened and initiate vesicle fusion and ACh release into the synaptic cleft. ACh binds postsynaptic receptors which open cation channels resulting in an end plate potential (depolarization). A single synapse is responsible for changes in the postsynaptic cell because ACh always depolarizes the postsynaptic membrane and always causes muscle contraction. ACh is eliminated by acetylcholinesterase which is located in the basal lamina.

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14
Q

Describe synapse transmission in the CNS as well as the two types of responses NT’s can induce and whether this response is dependent on properties of the NT or the receptor.

A

Presynaptic action potentials similarly result in calcium influx and vesicle fusion. Neurotransmitters bind postsynaptic receptors and initiate different effects depending on the properties of the receptor. Postsynaptic potentials are graded by the amount of NT binding and can be either excitatory or inhibitory. Excitatory synapses tend to be located on the dendrites while inhibitory synapses tend to be located on the cell body. Action potentials are not always elicited in the postsynaptic cell. Many EPSPs are usually required to generate a postsynaptic action potential. CNS synapses are more plastic than PNS ones.

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15
Q

What conditions affect the functioning of the presynaptic terminal?

A

Congenital myastehic syndromes that impair endocytosis or membrane recycling Lambert Eaton myastheic syndromes (affect presynaptic calcium channels) Botulinum and tetanus toxins impair vesicle fusion.

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16
Q

What is the difference between direct and indirect ligand gated ion channels?

A

Direct: the NT receptor is an ion channel that opens upon ligand binding Indirect: the NT receptor activates an ion channel in response to ligand binding via a second messenger system like a G-protein

17
Q

What three signaling properties determine whether or not an action potential will be generated in the CNS?

A

The decision to fire an AP or not depends on the location, strength, and sign (excitatory or inhibitory) of all of the inputs to the postsynaptic cell. If it is sufficient to reach threshold at the axon hillock, a postsynaptic action potential will occur.

18
Q

What is the membrane time constant?

A

The time constant is a passive property of the postsynaptic cell membrane which affects temporal summation of consecutive signals. It describes the amount of time required for the postsynaptic cell to return to resting membrane potential. A neuron with a long time constant will be easier to bring to threshold with consecutive excitatory inputs than one with a short time constant.

19
Q

What is the membrane length constant?

A

Length constant is a passive property of the post synaptic cell that affects spatial summation of consecutive signals. It is defined by how far the signal can travel before diminishing below threshold and depends on the distance to the axon hillock and the capacitance of the membrane. Neurons with a long length constant are more likely to be brought to threshold than those with short length constants.

20
Q

What are presynaptic inhibition and presynaptic facilitation?

A

Axo-axonic synapses can be modulatory in that they control how much neurotransmitter is released by regulating calcium influx. Signals that promote calcium influx (by inhibiting K+ channels that inhibit calcium influx) facilitate presynaptic transmission. Conversely, activating these K+ channels or increasing chloride conductance can decrease calcium influx. Direct inhibition of NT release is independent of calcium entry and can also result in presynaptic inhibition.

21
Q

Describe Wallerian degeneration in the PNS.

A

Wallerian degeneration involves Schwann cells unwrapping from the axon, fragmentation of the distal axon, and macrophages cleaning up axonal and myelin debris. Schwann cells maintain their relative positions along the degenerating axon and will divide during axon regeneration. Degeneration is important for healing and the hallmark of degeneration is the vanishing of the rough ER.

22
Q

Describe Wallerian degeneration in the CNS. How is it different than in the PNS?

A

Wallerian degeneration in the CNS is much slower–distal axon fragments and myelin debris persist much longer in the CNS. The neuron often completely degenerates and connected neurons are affected as well. This, along with inhibitory signals from the environment, results in poor regenerative capacity in the CNS.

23
Q

What is the difference between an electrical synapse and a chemical synapse?

A

Electrical synapse: ion channels

  • Fast, direct, all or nothing, stereotyped excitatory function
  • Do not allow inhibitory actions or plasticity

Chemical synapses: mediated by diffusion of neurotransmitters across a cleft

  • Flexible, complex, and plastic
  • Can be excitatory or inhibitory
  • Can amplify small signals
24
Q

Describe ionotropic transmission.

A

Ion channels: constitutes ionotropic transmission

  • Neurotransmitter binding allows ions to flow across an electrochemical gradient
  • Excitatory receptors are cation-selective channels (common NT: glutamate, ACh)
  • Inhibitory receptors are anion-selective channels (common NT: GABA, glycine)
  • Triggers action potentials
  • Altering channel subunits permits receptor diversity–different functions, expression during development, pharmacology, intracellular events, localization, etc.
25
Q

Describe metabotropic messaging.

A

G-protein coupled receptors: metabotropic signaling

  • G-protein activates a second messenger system in response to ligand binding
  • Monomers–no interchangable subunits
  • Act through GTP binding proteins that can activate or inhibit channels/enzymes
  • Effector protein can open a gated ion channel
  • Capable of amplifying or dampen signals via a second messenger system
  • Slower but can modulate synaptic input, trigger multiple downstream effects (gene transcription, ion channels, etc.), and are more sustained
26
Q

Briefly describe the characteristics of a neurotransmitter and their lifecycle.

A

Characteristics:

  • Specific method for synthesis
  • Specific release
  • Induces a post-synaptic effect
  • Has a method for inactivation

Life cycle:

  • Synthesis
  • Packaging
  • Release
  • Activation of receptors
  • Termination by diffusion, destruction, or re-uptake
27
Q

What are the four types of neurotransmitters? How else can they be classified?

A
  • Amino acids: glutamate, GABA, glycine
  • Small molecules: acetylcholine
  • Biogenic amines: catecholamines, serotonin, histamine
  • Peptides

Alternatively:

  • Excitatory: glu, ACh, 5-HT, histamine, catecholamines
  • Inhibitory: GABA, gly
28
Q

Describe glutamate transmission, including its normal site, the type of receptor it activates, how it is removed from the synapse, and it’s major role in the body.

A
  • Major excitatory neurotransmitter of CNS
  • Ionotropic receptors: NMDA (gates calcium and sodium), AMPA (gates sodium), and Kainate (pre- and postsynaptic and glial, gates sodium)
  • Metabotropic receptors: mGluRs are pre- and postsynaptic and glial and are linked to decreased cAMP levels
  • Reuptaken by neurons and glia
  • Critical for learning and memory
  • Excitotoxicity: seizures, hypoglycemia, ischemia, HIV
29
Q

What are NMDA and AMPA receptors?

A

NMDA receptors require both glutamate and glycine binding to open as well as postsynaptic depolarization to displace the Mg ion blocking the ion pore. Once open, they are permeable to Na, K, and Ca and produces more sustained currents that are resistant to desensitization. Blockers are used in PD, AD, anesthetics, and drugs of abuse.

AMPA receptors mediate fast excitation and their physiology is determined by their subunits. They desensitize with repeated stimulation.

30
Q

What are the major features of GABA and GABA receptors?

A

GABA is the main inhibitory neurotransmitter in the brain (not spinal cord). There are two ionotropic (Cl-) GABA receptors and one metabotropic receptor.

  • GABA-A receptor: mediates fast (ionotropic) synaptic inhibition in the brain; associated with epilepsy, anxiety, and addiction
  • GABA-B receptor: produces slow, long lasting inhibitory currents (metabotropic); drugs that work here include GHB and ecstasy
31
Q

What are the major features of acetylcholine and its two receptor types?

A

ACh is the major excitatory neurotransmitter of the PNS but plays a minor role in the CNS as well.

  • Nicotinic ACh receptors: ionotropic, gates cations, multiple subtypes exist
  • Muscarinic ACh receptors: metabotropic, found both pre- and postsynaptic in CNS, PNS, and organs

Cholinergic systems regulate dopaminergic systems (relavent to PD)

Myasthenia gravis is caused by antibodies to nAChR

32
Q

What types of receptors does serotonin bind? What clinical syndrome is it associated with?

A

Serotonin binds ionotropic and metabotropic receptors and is associated with depression.

33
Q

What are the catecholamines? What receptors do the bind? What diseases do they relate to?

A

Catecholamines bind metabotropic receptors

  • Dopamine: Parkinson’s, schizophrenia, pleasure/reward
  • Norepinephrine
  • Epinephrine