The cerebral cortex is a highly interconnected sheet of neurons that are constantly active and interacting. This ongoing interaction allows context-dependent complex behaviors to be generated by providing a mechanism for the rapid and dynamic modulation of neuronal responsiveness and flexible coupling of cortical neurons and networks. The generation and impact of cortical-cortical interactions depends upon a precise balance of recurrent excitation and inhibition. In-addition, information processing in the cortex depends critically upon the rate and timing of action potentials. The proposed projects will reveal the functional balance of recurrent excitation and inhibition in vivo and the cellular mechanisms by which the rate and timing of action potential generation is controlled, including during natural sleep and waking. The cortex is built to generate periods of persistent activity, such as during the operation of working memory, or in relation to selective attention. The mechanisms through which persistent, but at the same time rapid, changes in neuronal activity and responsiveness are generated in cortical networks will be investigated. The h-current has proven to be a very important contributor to network activity, through the control of communication between the soma and dendrites of single neurons. The important role of the h-current in persistent activity will be investigated. Finally, the mechanisms by which neuronal network discharge, such as with epileptic seizures, spontaneously stops will be examined with recordings from synaptically connected pairs of neurons. The possibility that synaptic depression or the activation of intrinsic ionic currents contributes to the natural, but temporary, cessation of epileptiform or sleep-related cortical bursts of activity will be examined. These studies will yield valuable information into the basic mechanisms by which cortical networks operate through recurrent excitation and inhibition and how this operation is prevented from being converted into the abnormal discharges of neurological disorders such as epilepsy.
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