Research Overview

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The thalamocortical circuit lies at the core of information processing in the central nervous system. During wakefulness, information is processed in a recurrent fashion from the periphery to prefrontal cortex through many parallel thalamocortical pathways that select, amplify and integrate features from sensory input while forming associations, predictions and motor commands. During sleep, the same circuitry generates the primary sleep rhythms believed to play a role in memory consolidation and performance improvement. Although many details of thalamocortical circuitry are known, little is understood about the processes in large-scale networks that produce conscious experience and sleep.

Large-scale detailed computer models of the thalamocortical system permit neural activity to be analyzed and manipulated in ways that are often impossible experimentally. Using the Synthesis simulator, I have constructed a model that reproduces experimental data from primary and higher-order visual cortices across multiple levels – from intracellular recordings to optical imaging to the EEG – during both wakefulness and sleep. This model is composed of over 65,000 regular spiking and intrinsically bursting neurons and over 8 million thalamocortical, corticothalamic, and both intra- and interareal corticocortical connections encompassing portions of two visual areas and associated thalamic and reticular thalamic nuclei. The connections are patterned according to cortical and thalamic microcircuitry and are governed by synapses that model the dynamics of AMPA, NMDA, GABAA and GABAB currents. Neuromodulatory influences representing diffuse cholinergic, noradrenergic, dopaminergic and serotonergic projections are modeled as changes in synaptic and cellular conductances. The model exhibits correlated ongoing activity reflecting the functional connectivity of the thalamocortical circuit. Visually evoked selective responses give rise to gamma-frequency synchronized oscillations and evolve according to short-term synaptic depression and intrinsic current dynamics. When the influence of diffuse neuromodulatory projections is withdrawn, the model transitions to a sleep-like state during which the individual cells undergo a slow oscillation synchronized at the population level, as observed in slow-wave sleep. Building on this work, a model of transcranial magnetic stimulation (TMS) in motor cortical circuitry has also been developed and validated, providing specific predictions about the activity generated in cortical networks due to a TMS pulse.

With these tools, I am investigating the role of spontaneous activity, oscillations and synaptic plasticity in the integration, acquisition and consolidation of information during both wakefulness and sleep.

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