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Decreased excitability of pyramidal tract neurons in layer 5B (PT5B) of primary motor cortex (M1) has recently been shown in a dopamine-depleted mouse model of parkinsonism. We hypothesized that decreased PT5B neuron excitability would substantially disrupt oscillatory and non-oscillatory firing patterns of neurons in layer 5 (L5) of primary motor cortex (M1). To test this hypothesis, we performed computer simulations using a previously validated computer model of mouse M1. Inclusion of the experimentally identified parkinsonism-associated decrease of PT5B excitability into our computational model produced a paradoxical increase in rest-state PT5B firing rate, as well as an increase in beta-band oscillatory power in local field potential (LFP). In the movement-state, PT5B population firing and LFP showed reduced beta and increased high-beta, low-gamma activity of 20-35 Hz in the parkinsonian, but not in control condition. The appearance of beta-band oscillations in parkinsonism would be expected to disrupt normal M1 motor output and contribute to motor activity deficits seen in patients with Parkinson's disease (PD)., Competing Interests: Potential Conflicts of Interest Nothing to report.

Depolarizing current injections produced a rhythmic bursting of action potentials - a bursting oscillation - in a set of local interneurons in the lateral geniculate nucleus (LGN) of rats. The current dynamics underlying this firing pattern have not been determined, though this cell type constitutes an important cellular component of thalamocortical circuitry, and contributes to both pathologic and non-pathologic brain states. We thus investigated the source of the bursting oscillation using pharmacological manipulations in LGN slices in vitro and in silico . 1. Selective blockade of calcium channel subtypes revealed that high-threshold calcium currents I L and I P contributed strongly to the oscillation. 2. Increased extracellular K + concentration (decreased K + currents) eliminated the oscillation. 3 . Selective blockade of K + channel subtypes demonstrated that the calcium-sensitive potassium current ( I A H P ) was of primary importance. A morphologically simplified, multicompartment model of the thalamic interneuron characterized the oscillation as follows: 1. The low-threshold calcium current I T provided the strong initial burst characteristic of the oscillation. 2. Alternating fluxes through high-threshold calcium channels and I A H P then provided the continuing oscillation's burst and interburst periods respectively. This interplay between I L and I A H P contrasts with the current dynamics underlying oscillations in thalamocortical and reticularis neurons, which primarily involve I T and I H , or I T and I A H P respectively. These findings thus point to a novel electrophysiological mechanism for generating intrinsic oscillations in a major thalamic cell type. Because local interneurons can sculpt the behavior of thalamocortical circuits, these results suggest new targets for the manipulation of ascending thalamocortical network activity.