(3) neuron structure & function

neuron structure & functional relationships, neuron function, action potential biology chemical synapse biology

what are the four main structural regions of a neuron and their specific functional roles in information processing

1. dendrites/postsynaptic terminal: receives information

2. soma (cell body): process information

3. axon: transmits information (action potential propagation)

4. presynaptic terminal: delivers info (NT release)

what sets the resting membrane potential of a neuron

K+ leak channels and the Na+/K+ ATPase pump set resting potential -70 mV

what is the diff in function between a graded potential and an action potential

• graded potential: small local voltage change in soma/dendrite (10-15 mV) - needed to reach threshold to AP

• action potential: large 90-100mV all or none wave driven by Na_V channels down the axon

what is the synaptic potential

when the action potential arrives at the synaptic terminus, it activates the synapse by triggering ion channels at the channel to RELEASE NT→ converting electrical wave into chemical signal for postsynaptic cell

what are the 6 phases of the action potential cycle? include how Na_v and K_v channels is involved in them

1. Resting state

   1. Both Na_V and K_V channels are closed

   2. voltage gradient caused by voltage-indepdt K+ leak channels and Na/K pump

2. stimulation (reach threshold)

   1. local graded potential depolarizes membr to threshold -55mV

3. depolarization

   1. voltage-sensing domain detect shift and rapidly OPEN Na_V channels

   2. massive Na+ influx shoot memb pot to +30 mV

4. peak (Na_V inactivation)

   1. protein domain (ball/chain) physically blocks inner Na_V pore

   2. this inactivated state creates the absolute refractory period - NO new AP can fire

5. repolarization

   1. Slower K_V channels fully open, fast K+ efflux to make internal -

6. late repolarization and recovery

   1. slower closing of K_V channel cause hyperpol overshoot

   2. hyperpol makes relative refractory period (strong stim can trigger AP)

   3. Na/K Atpase pump restores to -70mV

how do mutations that impair Na_V channel inactivation lead to epileptic conditions

channels stay open too long, leading to excessive Na+ influx, hyperexcitability, and rapid uncontrollable AP firing

what effect do antiepileptic drugs have on Na_V channel states to treat seizures

they stabilize the inactivated state, prolonging the absolute refractory period to reduce excessive AP firing frequency

what is the difference in absolute refractory and relative refractory?

• absolute refractory: membrane will NOT respond, no matter how strong the stimulus is

  • due to Na_V channel inactivation

• relative refractory: membrane will respond if stimulus is STRONG

  • due to slow closing of K_V channels

how does the refractory period determine the action potential frequencies

the refractory period is the required recovery time after an AP before cell can fire again aka cooldown

• SHORTER refractory period = MORE action potentials fired

what is the function and purpose of glial cells

• glial cells wrap their membranes around axon fibers to form the myelin sheath

• it provides INSULATION bc its high lipid/fat content prevents ion current from leaking out of axon membrane

what do schwann cells do

myelinates axons in the peripheral nervous system

what do oligodendrocytes do

myelinates axons in the central nervous system

how do demyelinating diseases (eg Multiple Sclerosis) disrupt neuron signaling

• the body’s immune sys destroys myelin insulation, causing electrical current leakage

• slows down or blocks AP conduction down axon

• cause motor impairment/sensory loss

what are the 2 factors affecting action potential speed

• myelination: provide electrical insulation, allowing fast saltatory conduction→ MORE myelin = FASTER

• axon diameter: LARGE diameter reduce internal electrical resistance, letting current flow FASTER down axon

what are the 3 types of nerve fibers and how fast do they conduct

1. Type A: large-diameter, myelinated → fastest (15-120m/s)

   1. motor neurons supplying skeletal/sensory neuron

2. Type B: medium-diameter, lightly myelinated → med speed (3-15)

   1. autonomic nervous sys (ANS)

3. Type C: small-diameter, unmyelinated → slowest (2 or less)

   1. ANS

how does action potential propagation work in unmyelinated axons

• AP must be regenerated at every single adjacent patch of membrane down axon length

• as current moves down axon, a fraction of the charge is lost due to K+ channels and leak channels

• because charge leaks out, it takes longer for adjacent membrane regions to reach threshold

how does action potential propagation work in myelinated axons (saltatory)

• lipid rich myelin insulate axons segment between gaps, preventing charge leaking out

• hits threshold much earlier - faster signals

• higher fidelity and speed for long nerve tract eg motor neurons from brain to peripheral muscles

what is the diff bt continuous and saltatory propagation

• continuous - unmyelinated axon

  • charge diffuse down but positive currents leaks out across membrane thru K+ channels → slow bc AP must be regen at little steps

• saltatory - myelinated

  • myelin sheaths insulate axon, decreasing K+ efflux and charge leak → fast bc current flows internally jumps directly bt nodes of ranvier

what is the 4 steps of the chemical synapse

1. action potential propagate rapidly to synaptic terminus from presynaptic area

2. chemical synapses let signal to be transmitted from one cell to next

3. chem synapse produce depolarization or other signal to next cell

4. chem-induced depol/other signal can trigger/modulate an AP in next cell

what does synaptotagmin do

it is the Ca²⁺ sensor, telling the SNARE complex ropes to pull up vesicle cargo up to FUSE with the membrane wall and release of NT into synaptic cleft

what does the SNARE complex do

acts as the physical “docking site” holding the neurotransmitter vesicle near the membrane

describe the 4 steps on how an AP triggers NT release at the presynaptic terminal and how signal gets shut off//resets for cholinergic synapses and adrenergic/dopaminergic synapses

1. AP arrival & calcium influx: opens voltage-gated Ca2+ channels, increasing local terminal Ca2+ lvl

2. vesicle docking & fusion: when Ca2+ binds synaptotagmin, it signals the SNARE complex to pull vesicle into membrane - fusion and release NT

3. termination of signal - cleaning up cleft

   1. CHOLINERGIC synapses

      1. (Ach is broken directly in enz by AChE→ chops ACh to acetate/choline to turn OFF signal)

   2. MONOAMINE synapses/ adrenergic/dopaminergic - G protein

      1. NOT degraded in cleft ; removed by monoamine transporters (MATs-NET, DAT, SERT) that use favorable Na+ grad to transport NT back in presynpatic cleft

4. resets - refill synaptic vesicles by…

   1. CHOLINERGIC synapses = VAT (vesicular acetylcholine transporter)

   2. ADRENERGIC/DOPAMINERGIC = VMAT (monoamine transporter)

How do the postsynaptic receptors differ between a cholinergic synapse and an adrenergic/dopaminergic synapse?

• cholinergic synapses use ionotropic receptors (nicotinic Ach receptors that open ion channels directly)

• adrenergic/dopaminergic synapses use GPCRs/metabotropic receptors (that activate G-proteins)

what is the most abundant neurotransmitter in the CNS

glutamate

what is the system, receptor, stimulus, and pathology of acetylcholine NT

• CNS/PNS

• GPCR/channel

• excitatory/inhibitory

• muscle

what is the system, receptor, stimulus, and pathology of norepinephrine NT

• CNS/PNS

• GPCR

• excitatory/inhibitory

• depression

what is the system, receptor, stimulus, and pathology of dopamine NT

• CNS

• GPCR

• excitatory/inhibitory

• parkinson’s

what is the system, receptor, stimulus, and pathology of serotonin (5-HT)

• CNS

• GPCR/channel

• excitatory/inhibitory

• depression

what is the system, receptor, stimulus, and pathology of glutamate NT

• CNS

• GPCR/channel

• excitatory

• stroke

what is the system, receptor, stimulus, and pathology of GABA NT

• CNS

• GPCR/channel

• inhibitory

• anxiety

what are the two ways neurotransmitters act on target cells

1. excite cells by inducing membrane depolarization (ACh or glutamate), move CLOSER to threshold

2. inhibit cell by hyperpolarizing the membrane (GABA—Cl- channels), move FARTHER from threshold

what is integration

multiple inputs can influence response of the target neuron

what is summation in a neuron

• added effect of all graded potentials (from EPSP) in the neuron’s soma

  • determines whether AP is fired or not

how do you reach threshold with multiple EPSPs

synapses should fire closely in time to reach threshold

what is IPSP

inhibitory post synaptic potential → hyperpolarized

what is EPSP

excitatory post synaptic potential - depolarized

what are the 6 steps of vesicle NT release regulation

1. in presynap neuron, some vesicles are docked onto membrane while large reserve pool of vesicles are found deeper in neuron

2. AP travels through axon and reaches presynap term → activates Ca2+ channels to let Ca2+ in

3. Ca2+ diffuses inside cell → BINDs to synaptotagmin of SNARE complex

4. activated synaptotagmin activates fusion of vesicle and plasma membrane → NT flows OUT to synaptic cleft

5. once emptied, vesicle fuses w plasma membrane

6. fused vesicles are replaced by other vesicles

what is long-term potentiation vs long-term depression

• LTP grows dendrites & strengthens synaptic connections

• LTD weakens connections

how is long term potentiation and depression triggered

• LTP = strong, repeated glutamate stimulation

• LTD = weaker, low frequency stimulation

what are the 4 steps of long term potentiation

1. glutamate BINDS to AMPARs to let Na+ in

2. cell depolarization ACTIVATES NMDARs and let plenty Ca2+ in

3. activates specific kinases that increase # of AMPARs on cell surface

4. more AMPARs = more glutamate sensitivity = stronger synaptic response

what are the 5 steps of long term depression

1. glutamate BINDs to AMPARs to let Na+ in

2. cell depol ACTIVATES NMDARs, letting smaller/weaker amt Ca2+ in

3. activates ALTernate pathway that ACTIVATE a phosphatase

4. phosphatase DEPHOSPHORYLATE AMPARs, pulling AMPARs OUT of membrane

5. less AMPARs on surface = low glutamate sensitivity = weaker synaptic response

what do neuromodulators do

change release of NT or postsynaptic cell response

how does presynaptic inhibition work

• one neuron reduce NT release of another neuron

• one neuron will release GABA that binds to GABA receptors of target neuron

  • as AP of target neuron arrives to presynap term, membrane is HYPERPOLARIZED to INACTIVATE Ca2+ channels

  • less Ca2+ enter target neuron → less NTs are released → postsynap neuron gets REDUCED EFFECT

• exerts anti-anxiety effect

how does presynaptic facilitation work

• neuron increases NT release of another neuron

• one neuron will releae SEROTONIN that binds to serotonin receptors of target neuron

  • serotonin will activate MORE Ca2+ channels to increase Ca2+

  • MORE NTs are released → postsynaptic neuron gets INCREASED EFFECT

• exerts anti-depressive effect

where are most drug target sites located on the neuron

localized to the synaptic terminus