Thalamocortical Physiology Flashcards
Understand why the thalamus, which is a deep structure and therefore cannot contribute directly to the EEG, does contribute to the signals recorded in an EGG.
The contribution of thalamus to EEG recording is due to thalamocortical connections.
All sensory information is relayed through the thalamus before synapsing in the cortex. EEG cannot pickup the electrical signals directly from the thalamus (these neurons are too deep given that recordings are taken from the scalp), but because the thalamus projects to the cortex, EEG measurements of cortical activity provide insight into function at the level of the thalamus. EEG recordings at the cortical level require simultaneous firing of many cortical cells with parallel orientation. So it is the synchronous synaptic input from the thalamus on the cortical neurons that is best evaluated by EEG.
Understand that thalamic relay neurons have conductances that endow them with the ability to respond to a hyperpolarization with slow Ca2+ spikes that fire at a frequency of ~3 Hz (the delta frequency). Riding on top of the Ca2+ spike are several action potentials. Understand the role of the T-type Ca2+ channel in the generation of the slow Ca2+ spike.
When you are awake, there is very little inhibition of the thalamic relay nuclei by the reticular cells. As a result, the resting membrane potential is relatively depolarized (-55mV) and action potentials are fired rapidly due to opening of voltage-gated sodium channels. T-type calcium-channels in the membrane of the thalamic relay neurons are inhibited by depolarization, so their inactivation gates are closed when awake (at -55 mV).
When you are in the slow wave stage of sleep, reticular cells are inhibiting thalamic relay neurons and the membrane potential is hyperpolarized at -85 mV. At this potential, the calcium channels are activated and Ca2+ flows into the neurons creating a slow action potential.
As the Ca2+ flows in, voltage-gated sodium channels are opened. The net result is a series of Ca2+ spikes with several fast action potentials on top of the Ca2+ spikes (resulting from depolarization through Na+ channels).
These calcium spikes have a frequency of 3 Hz. This 3 Hz pattern is referred to as the delta wave and is the characteristic pattern of slow wave sleep.
Understand that unless thalamic relay neurons are hyperpolarized by inhibitory interneurons in the thalamic reticular nuclei the thalamic relay neurons cannot fire the
slow Ca2+ spikes that give rise to the slow delta wave recorded in the EEG during slow wave sleep
T-type Ca2+ channels are inactivated by depolarization (inactivation gates are closed). As a result, they cannot fire action potentials unless they are hyperpolarized. Hyperpolarization and the production of slow Ca2+ spikes occurs when the thalamic relay neurons are inhibited by thalamic reticular cells. The reticular cells inhibit the thalamic relay neuron and hyperpolarize the cell to around -85 mV.
Understand how thalamocortical connections -between the thalamic relay neurons and the pyramidal cortical neurons- are such that the Ca2+ spikes occurring in thalamic relay neurons at the delta frequency give rise to a slow wave in the delta frequency in the EEG.
Thalamic relay neurons form excitatory, glutamatergic synapses on the cortical neurons. The slow Ca2+ spikes in the thalamic relay neurons are carried to the synaptic terminal, resulting in the release of glutamate. Glutamate excites the cortical neuron. So every time a Ca2+ spike is fired in the relay neuron, the AP is propagated to the synapse, glutamate is released and an AP is fired in the cortical neuron. The AP in the cortical neuron is of the same frequency of the relay neuron, generating a slow wave that is detectable by EEG.
Discuss how the slow EEG waves recorded in absence epilepsy (at the δ frequency ~3Hz) are thought to stem from thalamocortical oscillatory activity.
Absence epilepsy is characterized by sudden staring spells and absence of activity. During these episodes, brain EEGs look very similar to those of a person in slow wave sleep (a 3 Hz delta wave). It is thought that these patterns occur abnormally while the patient is awake due to defects in the T-type Ca2+ channels on the thalamic relay nuclei.
Understand that ascending brainstem circuits sending axons to the thalamus regulate the thalamocortical circuit. Know that when the cholinergic cells of the reticular activating system are stimulated the animal awakes from sleep and the corticothalamic slow waves stop.
Thalamocortical circuit is regulated by axons ascending from the brainstem
Regulation occurs via cholinergic, noradrenergic and serotonergic neurons
*Cholinergic neurons from the reticular activating system (neuronal circuits between brainstem and cortex through thalamus): stimulation leads to ACh release into thalamus and awakening from sleep and disruption to slow waves in EEG
*Noradrenergic neurons from the locus coeruleus (a nucleus in the pons responsible for responses to stress and panic): stimulation during “flight or fight” response leads to noradrenaline release into thalamus
o Serotonergic neurons from the raphe nucleus (serotonin-releasing nucleus in brainstem): release serotonin into thalamus and plays a role in sleep/wake cycles
How do the drugs valproic acid and ethoxosuximide treat epilepsy
Absence epilespy is a mutation in the T type Ca2+ channels. Both Valproic and Ethosuximide inhibit T type Ca2+ channels.
Understand why a mutation in the T type Ca2+ channel could give rise to this type of epilepsy.
Normally, this channel is inactivated by the depolarized (-60 mV) membrane potential that exists in persons while they are awake. But in patients with absence epilepsy, the channel is no longer inhibited by depolarization. The inactivation gate is abnormally open at depolarized resting membrane potentials. As a result, Ca2+ spikes that are normally characteristic of slow phase sleep are fired while the patient is awake. There is a predisposition for absence seizures in families with T-type Ca2+ channel mutations.
