FBIimaging · Organization of long-range inputs in sensory cortex for top-down modulation of tactile perception

The sensory cortex plays a crucial role in detecting and interpreting environmental stimuli. Tactile inputs from the peripheral organs are transmitted through the thalamus to the primary somatosensory cortex (S1), where they are integrated with long-range projections from higher-order brain regions, defined as feedback (top-down) inputs. Top-down control has been proposed to mediate contextual or attentional modulation of sensory processing. The host laboratory has shown that layer 5 pyramidal neurons (L5-PNs) in S1 exhibited dendritic regenerative potentials, so-called calcium spikes, when mice detect tactile stimuli, and their manipulation altered the mouses perception threshold. Interestingly, the L5-PNs distal-apical dendrites, where calcium spikes originate, are extensively innervated by axonal projections from higher-order cortical and thalamic areas. In light of this evidence, I hypothesize that long-range inputs to S1 modulate tactile detection via facilitating dendritic calcium spikes in L5-PNs. To test this hypothesis, I will determine the localization and timing of the long-range feedback inputs reaching the apical dendrites of S1 L5-PNs, which covary with the tactile detection sensitivity. Furthermore, I will test the context dependence of the long-range inputs. I will employ a whisker detection paradigm, where mice are trained to detect single whisker deflections to obtain water rewards. I will combine one-photon wide-field imaging and state-of-the-art genetic tools to visualize the glutamatergic inputs in distal dendrites or the axonal calcium activity in long-range projections. My study will provide new insights into the neuronal mechanisms underlying contextual modulation of perception by shedding light on the integrative properties of cortical pyramidal neuron dendrites.