Cellular and Circuit Properties of Slow Oscillations In The Thalamic Reticular Nucleus

<p>During sleep, neurons in the thalamic reticular nucleus (TRN) generate distinct types of oscillatory activity. While the reciprocal synaptic circuits between TRN and sensory thalamic nuclei underlie the generation of sleep spindles, the mechanisms regulating slow (<1 >Hz) forms of thalamic oscillations are poorly understood. Under <em>in vitro</em> conditions, in the absence of synaptic inputs, TRN neurons can generate slow oscillations in a cell-intrinsic manner. Activation of postsynaptic Group 1 metabotropic glutamate receptors (mGluR) leads to long-lasting plateau potentials thought to be mediated by both T-type calcium currents and calcium-activated nonselective cation currents (I_CAN). However, the identity of I_CAN and the possible contribution of thalamic circuits to slow rhythmic activity remain unclear. Using intracellular recordings of neurons in thalamic slices derived from adult male and female mice, I recorded slow forms of rhythmic activity in TRN neurons. Slow oscillations were driven by fast glutamatergic inputs from thalamic relay neurons, but did not require postsynaptic mGluR activation. For a significant minority of TRN neurons (33%), synaptic inputs or brief depolarizing current steps led to plateau potentials and persistent firing (PF), and in turn, resulted in persistent synaptic inhibition in postsynaptic relay neurons of the ventrobasal thalamus (VB). Pharmacological approaches indicated that plateau potentials were triggered by calcium influx through T-type calcium channels and mediated by calcium and voltage-dependent transient receptor potential melastatin 4 (TRPM4) channels. Taken together, my results suggest that thalamic circuits can generate slow oscillatory activity, mediated by an interplay of TRN-VB synaptic circuits that generate rhythmicity and TRN cell-intrinsic mechanisms that control PF and oscillation frequency.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2020

Authors dc:creator

• O'Malley, John
• <p>0000-0003-3774-1702</p>

Contributors dc:contributor

• Michael Beierlein, Ph.D.
• Ruth Heidelberger, M.D., Ph.D.
• M. Neal Waxham, Ph.D.

• TRN
• TRPM4
• Thalamus
• Slow Wave Sleep
• Slow Oscillations
• Medicine and Health Sciences
• Molecular and Cellular Neuroscience

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1023

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2075