This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Of all human brain regions, none is more closely linked with our uniquely human qualities than the cerebral cortex; understanding the workings of the cerebral cortex is therefore a prerequisite for understanding ourselves as individuals and as a species, and is of immense clinical importance. The cerebral cortex receives, via the thalamus, the majority of incoming sensory information from the auditory, visual and somatosensory modalities, and is ultimately responsible for transforming these sensory inputs into the conscious experience we call perception. Identifying the fundamental components of the thalamocortical network and elucidating their synaptic connections is therefore a prerequisite for understanding the cortical computations leading to sensory perception. About 75-80% of all cortical neurons are either pyramidal or spiny stellate cells, excitatory neurons using glutamate as a neurotransmitter; the rest are GABAergic inhibitory interneurons. GABAergic interneurons within the thalamo-recipient layers (layer 4 and the layers 5/6 junction) are strongly excited by thalamocortical inputs, thereby eliciting in their target neurons feedforward inhibition that constrains their firing in time and space, and enhances the signal-to-noise ratio of the spatiotemporal cortical activation patterns representing the sensory event. About two-thirds of all cortical inhibitory neurons belong to two non-overlapping neurochemical groups: parvalbumin-containing interneurons and somatostatin-containing interneurons. Parvalbumin-containing interneurons are 'fast spiking' neurons, and are thought to synapse mostly on somata and proximal dendrites, while somatostatin-containing interneurons are often 'low-threshold spiking' neurons, and seem to prefer distal dendritic targets. These striking differences in intrinsic properties and synaptic targeting strongly suggest that these two subclasses may play quite distinct roles in thalamocortical computations involved is sensory processing. The goal of the proposed study is to test this hypothesis by comparing the electrophysiological properties and the underlying structural basis of feedforward inhibition elicited by these two interneuronal subtypes, and thus for the first time illuminate the differential roles played by specific subclasses of GABAergic interneurons during cortical processing of sensory-related inputs.
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