Author ORCID Identifier


Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation


Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Michael Beierlein, Ph.D.

Committee Member

Ruth Heidelberger, M.D., Ph.D.

Committee Member

M. Neal Waxham, Ph.D.

Committee Member

Harel Z. Shouval, Ph.D.

Committee Member

Jeannie Chin, Ph.D.

Committee Member

Michael Lorenz, Ph.D.


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 in vitro 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 (ICAN). However, the identity of ICAN 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.


TRN, TRPM4, Thalamus, Slow Wave Sleep, Slow Oscillations



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