PROJECT SUMMARY
Nearly all sensory signals enter the neocortex by way of the thalamus, and the sensory cortex, in turn, distributes
this information to several downstream cortical and subcortical areas. A prominent but often neglected feature
of the sensory cortex is numerous feedback projections from other cortical areas. This key organizational feature
of the brain implies that the ongoing activities in other cortical regions may influence local information processing
and the outputs of the sensory cortex. Indeed, corticocortical communication is thought to mediate cognitive
processes such as attention, prediction, expectation, and awareness. Communication problems between cortical
areas are also associated with certain neuropsychiatric disorders, including epilepsy, autism, and schizophrenia.
Despite its obvious importance, a thorough understanding of how cortical feedback activity influences sensory
processing has been elusive. The central goal of this investigation is to determine how long-range cortical
feedback projections influence cortical sensory processing at the level of cellular, synaptic, and circuit
mechanisms. We address this goal in three specific aims using the mouse sensorimotor system, a leading model
for studying forebrain circuits and active sensation. Aim 1 will focus on the connections between the motor cortex
and layer 2/3 of the somatosensory cortex. Using specific Cre-expressing mouse lines and optogenetics, we will
test the hypothesis that motor feedback engages two parallel but dynamically distinct systems of inhibition in
layer 2/3 of the somatosensory cortex. Aim 2 will focus on infragranular layers, which contained a mixed
population of excitatory projection neurons. Using both isolated and intact brain preparations, we will test the
hypothesis that the dynamic balance of excitation and inhibition caused by motor cortex activity is dramatically
different across deep-layer projection neurons depending on their cortical and subcortical projection target. Aim
3 will use optogenetics to unravel the inhibitory circuits mediating motor integration in layer 5/6 of the
somatosensory cortex. This project will provide much-needed insight into how cortical feedback systems
influence sensory processing. Such information will be essential for understanding neuropsychiatric disorders
involving feedback communication.