Great strides have been made recently in understanding cerebral cortical microcircuits. The introduction of transgenics and optogenetics together with advances in patch clamp techniques, have been instrumental in the rapid rate of discovery. For example, we now know there are at least three types of inhibitory interneurons in the cerebral cortex: those that express the Ca++ binding protein parvalbumin (PV), and those that use either the peptide neuromodulator vasoactive intestinal peptide (VIP) or somatostatin (SOM). Uniquely labeling these neurons reveals that these inhibitory interneurons exist in most areas of cerebral cortex. They have different morphologies, terminate on different parts of output neurons, have differing synaptic strengths and they play different roles in information processing. In this application, we propose to capitalize on the recent advances in transgenics and optogenetics to reveal the structure and function of inhibitory microcircuits within the superior colliculus and the role external inputs play in modulating these circuits. We have three aims. First, determine the physiology and targets of the local parvalbumin (PV) expressing neurons in the visuosensory layer of the collicular microcircuit. These experiments will test the hypothesis that PV neurons provide the dominant source of inhibition on sensory neurons that give rise to the colliculo-pulvinar-cortical pathway and to the descending intralaminar pathway to the motor layer. Second, determine the physiology and targets of extrinsic GABAergic inputs from the substantia nigra pars reticulata (nigra) to the motor layer collicular microcircuit. These experiments will test the hypothesis that external inhibition from the nigra is the dominant source of inhibition on motor output neurons in the superior colliculus microcircuit. Third, determine the function of the PV and nigral GABAergic inputs to collicular microcircuits. We will test the hypothesis that inhibition from PV neurons and inhibition from the nigra play different roles in determining response gain of collicular neurons in sensory and motor neurons. Because PV neurons have been implicated in neuropsychiatric disease processes the results of our experiments should clarify how these neurons contribute to higher mental function.
A sine qua non of higher mental function is our ability to make decisions. Extreme fluctuations in choice behavior may underlie certain neurological and psychiatric diseases such as schizophrenia, attention deficit disorder, Tourette Syndrome and obsessive compulsive disorder. A deeper understanding of the microcircuits underlying higher mental function such as choice and decision-making may lead to better diagnostics, better ways to assess therapies and should provide important insights into the mechanisms of symptomology in these disease states.
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