Neurobiology Exam 1

astrocytes

only in CNS, maintain ionic environment for signaling, form BBB, secrete growth factors for construction of new synapses

physiological vs. reactive astrocyte functions

physio - "good", provide trophic support

reactive - "bad", active neurotoxicity, form scars, increase inflammation

microglia

immune cells of the nervous system

- remove cellular debris from injury, secrete cytokines to modulate inflammation

oligodendrocytes

myelinate neurons in the CNS, provide trophic support, can myelinate multiple segments at once

Schwann cells

myelinate neurons in the PNS, can only myelinate one segment

receptive part of the neuron

dendritic zone

conducting part of the neuron

axon

convergence

the number of inputs to a single neuron

ex: sensory neurons

divergence

number of neurons innervated by a single neuron

ex: motor neurons

What is the significance of axodendritic or axoaxonic synapses?

they are usually inhibitory neurons

What maintains the electrical gradient in and out of the cell?

ion pumps, require ATP

What determines the cell's resting membrane potential?

permeability of different ions

- the RMP is closer to the potential of K+ because the cell is more permeable to potassium at rest

Nernst equation

used to determine membrane potential across a membrane only permeable to one ion

- depends on temperature, constants, and concentrations in and out of the cell

Goldman-Hodgkin-Katz equation

the membrane potential is affected by the relative permeability to each ion

If the permeability to a certain ion _____, the membrane potential moves closer to the equilibrium potential for that ion.

increases

Why is the resting membrane potential -70mV?

leaky potassium channels allow potassium ions to leak out which generates a negative charge on the inside of the cell

How do neurons encode information?

via electrical signals that result from transient changes in the RMP

generator/receptor potential

local, non-propagated response that occurs in some sensory receptors (mechanical --> electrical)

- graded: the larger the stimulus, the larger the depolarization

- additive: stimuli close together can produce a potential larger than one made by one stimulus

all-or-none law of action potentials

the amplitude of the action potential is independent of the magnitude of the current that caused the AP

rate law of action potentials

intensity of an AP is coded by the frequency of APs

selectivity filter of an ion channel

discriminates among ions

gate of ion channel

moves from a closed conformation to an open one in the presence of a certain stimulus

ligand-gated

ligand binds and channel opens

- convert chemical signal to electrical information

ex: excitatory nt binds to a sodium channel to open it

mechanically gated

mechanical force leads to gate opening

ex: sensory receptor for

pressure

ex: Piezo, 3 blades

voltage gated

change in voltage opens gate

ex: depolarization opens sodium channels

thermosensitive channels

ex: TRVP1

- contribute to sense of pain and body temperature

- heat changes fluidity of phospholipid layer, proteins detect this change

Describe how ion channels work.

1. Ion enters water-filled pore.

2. Selectivity pore (different amino acids) selects for ions.

ex: negative amino acids select for positive ions

Describe how the potassium channel works.

1. Voltage sensor senses changes in voltage.

2. When the cell depolarizes, the positive amino acids in the sensor domain are repelled and the channel closes.

3. When the cell repolarizes, the positive amino acids in the sensor domain are attracted and the channel opens.

Epilepsy - ion channels

Sodium channels are inhibited

- inhibitory neurons are unable to cause inhibition of APs

- leads to uncontrolled firing

Cerebellar ataxia - ion channels

impair action potential repolarization, leads to loss of voluntary movement, no new APs can be received

Migraine- ion channels

increases current flowing through calcium channels

local anesthesia

prevent pain signals from reaching the brain by blocking sodium channels

regional anesthesia

inject anesthetics into epidural space

general anesthesia

ketamine: blocks excitatory synapses

sedative: enhances GABA receptors

What happens when a neuron reaches threshold voltage?

sodium channels open quickly, potassium channels open slowly

depolarization

sodium channel voltage sensor senses change in voltage and opens, sodium flows in following its electrochemical gradient

repolarization

ball-and-chain mechanism shuts off sodium channel (sodium can still get into pore, just not into cell), potassium channels finally open (they were triggered by threshold but are just slow to open), potassium flow out with its gradient

hyperpolarization

potassium channels are slow to shut, potential continues toward that of the potassium

absolute refractory period

ball-and-chain mechanism blocks sodium channel, the cell is not receptive to any more sodium so another AP cannot occur even though the depolarization is bidirectional

relative refractory period

voltage-gated sodium channels are in the process of resetting, an action potential is only possible with a stronger than normal stimulus

When is the cell most permeable to potassium?

at rest, leaky channels determine RMP

When is the cell most permeable to sodium?

during depolarization

two ways to increase conduction velocity

increase axon diameter, insulate the axon with myelin (prevents current from leaking out of the axon)

saltatory conduction

the action potential doesn't have to excite every point of the axon, just the Nodes of Ranvier (sodium only enters here)

How does increased diameter influence internal resistance of an axon?

decreases internal resistance which leads to higher conduction velocity

How does myelination influence the membrane resistance?

increases resistance and prevents current from leaking out of the membrane, current is pushed down the axon

How do oligodendrocytes and Schwann cells offer trophic support to neurons?

they offer nutrients through cytoplasmic contact with the axons

risk factors of MS

EBV, smoking, vit D deficiency, genetics

signs and symptoms of MS

monocular blindness (optic neuritis), motor weakness (lesions on corticospinal tracts)

pathology of MS

myelin sheaths are degraded leaving the neuron exposed to T lymphocytes that migrate from the PNS, the neurons lose trophic support

electrical synapse

neurons physically connected by connexons (gap junctions) expressed on both active sites of the neurons, ions pass directly through the connexons and the action potential propagates, communication is bidirectional

functions of electrical synapses

fast transmission, bidirectional communication

ex: important for regulation of rhythmic movements like breathing (brainstem)

chemical synapse

neurons are not physically connected, vesicles with neurotransmitters are released and bind to ligand-gated channels on the postsynaptic cell

signaling transmission at chemical synapse (steps)

1. synaptic vesicles are filled with neurotransmitter

2. AP arrives at axon terminal and triggers calcium influx through voltage-gated channels.

3. Calcium influx causes exocytosis of vesicles

Where are neuropeptides synthesized?

soma of neuron, transported down axon

Where are small-molecule neurotransmitters synthesized?

in the presynaptic terminals

mechanism of synaptic vesicle cycling

1. coating with clathrin

2. vesicle enters cell

3. synapsins connect numerous vesicles for storage

4. kinases phosphorylate connections between storage vesicles

5. SNARE proteins on vesicle and membrane form docking complex at axon terminal

6. Calcium binds to synaptotagmin which causes the membrane to bend and for exocytosis of the vesicle to occur

endocytosis of vesicles

coated with clathrin, actin pushes the vesicle into the cell, auxillin and Hsp70 uncoat vesicle

EPSP

usually glutamate as the nt, brings the voltage closer to threshold to increase the likelihood of an action potential

IPSP

usually GABA, brings voltage further away from threshold to decrease the likelihood that an AP occurs

pathologies associated with vesicles

a. vesicles may be smaller than normal and carry less nt --> have less effect at synapse

b. absence of calcium channels --> no vesicle release

Where are neuropeptides synthesized?

in the soma

Which type of neurotransmitter mediates a fast response?

small molecule, neuropeptides tend to modulate slower, ongoing neuronal functions

small clear core vesicles

carry small molecule neurotransmitters

Where are small molecule neurotransmitters synthesized?

at the axon terminal

ex: glutamate, GABA, acetylcholine, serotonin, histamine

large dense-core vesicles

carry neuropeptides, larger to accommodate for larger cargo size

ionotropic

ligand-gated, neurotransmitter binds, channel opens, ions can flow through channel

metabotropic

second messenger system, can be inhibitory or excitatory depending on the G protein

effects of second messenger systems

can effect protein production or ion channel opening/closing

function of AcH in the brain

cholinergic neurons in the cerebellum, associated with Parkinson's, AcH is a major excitatory neurotransmitter in the PNS

ACh synthesis, release, degradation

1. ACh made from acetyl CoA and choline

2. VAChT loads vesicles with ACh

3. vesicles released upon calcium spark

4. AChE breaks ACh down into acetate and choline

5. choline reenters presynaptic cell through sodium cotransport through ChT

How do organophosphates affect ACh?

they are AChE inhibitors, cause paralysis

nicotinic receptors

ionotropic ACh receptors

muscarinic receptors

metabotropic ACh receptors, slow postsynaptic response

glutamate synthesis, release, degradation

1. glutamate made from glutamine in the mitochondria by glutaminase

2. VGLUTs package vesicles with glutamate

3. glutamate released

4. EAATs remove glutamate from synapse and transport it into glia cells

5. glutamate is converted back to glutamine via glutamine synthetase

6. glutamine is transported from glia to the presynaptic neuron via SN1 and SAT2

Why must glutamate be synthesized in the neuron from a precursor?

glutamate is a nonessential AA that cannot cross the BBB, glutamine can

What is the most excitatory nt in the CNS?

glutamate

How can reactive astrocytes cause neuron death with glutamate?

reactive astrocytes do not express EAAT to remove glutamate from the synapse, causes continual excitation that increases calcium in the postsynaptic cell --> apoptosis

AMPA

glutamate receptor, four subunits, ionotropic, generates fast and large currents

NMDA

glutamate receptor, ionotropic

- initial depolarization from AMPA cause magnesium to move from blocking the NMDA channel

- cations pass through

What is the role of glycine in NMDA?

glycine can hold the channel open for a longer period of time

mGluRs

cause slower postsynaptic responses that can excite or inhibit postsynaptic cells, identical dimers

GABA synthesis, release, and degradation

1. glucose metabolized to GABA throguh glutamic acid dehydrogenase

2. VIAAT loads vesicles with GABA

3. GABA can enter glial cells or the presynaptic cell through sodium co-transport

What vitamin does GAD use to synthesize GABA? What can a deficiency of this vitamin cause?

B6, infantile seizures (lack of inhibition)

ionotropic GABA receptors

cause influx of chloride ions that hyperpolarize the postsynaptic cell

effect of benzodiazepine and barbiturates

increase GABAnergic transmission

- reduce anxiety, sleep inducer, anesthetic

metabotropic GABA receptors

activates potassium channels (flows out to hyperpolarize the cell) and blocks calcium channels (no release of vesicles)

glycine synthesis, release, and degradation

1. synthesized from serine in the mitochondria

2. VIAAT load vesicles with glycine

3. vesicle released

4. Glycine from synapse can enter glial cell or presynaptic cell through sodium co-transport

What are some effects of mutations in glycine transporters?

lethargy, absence seizure, mental retardation

- increases inhibitory effects

Where is glycine most involved?

spinal cord and PNS

Glycine receptors are ligand-gated _____ receptors.

chloride

What do biogenic amines affect?

mood and behavior

- most psycho drugs affect the catabolism, action, or synthesis of these

dopamine

- motor functions in substantia nigra

- synthesized from tyrosine and DOPA

- VMAT stuffs vesicles with dopamine

- dopamine from synapse is transported with sodium into glia

- MAO in mitochondria and COMT in cytosol catabolize dopamine

How do cocaine and amphetamine affect dopamine?

inhibit DAT and increase dopamine concentration in the synapse --> psychosis, altered reality

Parkinson's and dopamine

dopaminergic neurons in the substantia nigra degenerate and lead to decreased motor control

noradrenaline

- forebrain, sleep/wakefulness, arousal, attention

- synthesized from tyrosine

- VMAT loads vesicles with NE

- released into synapse

- NET transport NE back into presynaptic cell

- MAO and COMT for degradation

adrenaline

- lateral tegmental system and medulla

- functions in respiration and cardiac function

- synthesized from tyrosine

- VMAT

- MAO/COMT

histamine

-arousal and attention

- made from histidine via histidine decarboxylase

-VMAT, MAO and histidine methyltransferase break down H at synapse

Where are histamine receptors found?

gut and vestibular system (motion sickness)

5-hydroxytryptamine

(serotonin)

- made from tryptophan

- in forebrain for sleep/wakefulness

- has metabotropic and ionotropic receptors

- SERT transports serotonin back into the neuron

- MAO