Lecture 25: Mechanisms of Bursting and Tonic Firing in Thalamocortical Neurons

What do thalamic relay cells do?

relay signals from the thalamus up to the cortex

Where are the cell bodies and axon terminals of thalamocortical neurons?

• cortex: axon terminals

• thalamus: cell bodies

True or False: Thalamocortical neurons switch between bursting and tonic firing.

true

What is burst/oscillatory mode and tonic firing link to?

different sleep/wake states

What is the Vm in slow wave sleep/deep sleep?

relatively hyperpolarized

What is occurring during slow wave sleep/deep sleep?

TC cells spontaneously generate bursts

What is the Vm in waking or REM sleep?

depolaried

What is occurring during waking or REM sleep?

burst charges abolished and cells fire repetitively

What do HCN channels stand for?

hyperpolarization-activated, cyclic nucleotide-gated cation channels

What do HCN channels play critical roles in?

• cardiac electrophysiology

• rhythmic firing of neurons in the brain

What are HCN channels permeable to?

both Na+ and K+ ions

What are the two kinetically classified Ca2+ channels?

• L-type

• T-type

What are the L-type channels?

• N

• P/Q

• R-type

What is the type of AP phase present in L-type channels?

long-lived plateau AP phase

What do L-type channels cause?

increase Ca2+ influx for contractile and secretory responses (e.g., neurotransmitter release)

What do T-type channels stand for?

transient

What are T-type channels activated at?

more negative voltages

What are T-type channels important for?

• AP initiation

• repetitive firing in cardiac cells and neurons

What are the two mechanisms of channel closing?

• deactivation

• inactivation

What happens if the stimulus is removed/Vm moves to potential not favorable for channel to be open?

deactivation

What happens if the stimulus is still present/Vm still within range favorable for channel opening?

inactivation

What is the mechanism for ion channel inactivation?

ball-and-chain mechanism

Describe the ball-and-chain mechanism.

• the N-terminal domain ball moves in and blocks the channel

• the B subunit moves in and blocks the channel

What is the mechanism of TC neuron rhythmic burst firing?

1. Ih (HCN channels) opened at hyperpolarized Vm values (below -60 mV)

2. cation influx through HCN channels depolarizes Vm to threshold for T-type Ca2+ channel activation (-65 mV)

3. depolarization of Vm past AP threshold (-55 mV) triggers AP firing

4. IT inactivation and Ih deactivation repolarizes Vm

5. Vm becomes sufficiently hyperpolarized to remove IT inactivation

What is the duration and number of spikes of each burst dependent on?

the IT kinetics

What does prolonged IT equate to?

more spikes per burst and longer burst duration

What persists when AP firing is blocked?

subthreshold oscillations

True or False: The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons.

true

With only INa and IK, what does the stimulated neuron generate?

a short train of APs in response to depolarization

What Is IC?

Ca2+-activated K+ current

What is IA?

A-type K+ current

What is IM?

muscarine-sensitive K+ current

What is IAHP?

slow afterhyperpolarization

What is IT?

T-type Ca2+ current