@article {SlaterENEURO.0256-20.2020, author = {Bernard J. Slater and Jeffry S. Isaacson}, title = {Interhemispheric callosal projections sharpen frequency tuning and enforce response fidelity in primary auditory cortex}, elocation-id = {ENEURO.0256-20.2020}, year = {2020}, doi = {10.1523/ENEURO.0256-20.2020}, publisher = {Society for Neuroscience}, abstract = {Sensory cortical areas receive glutamatergic callosal projections that link information processing between brain hemispheres. In primary auditory cortex (A1), ipsilateral principal cells from a particular tonotopic region project to neurons in matching frequency space of the contralateral cortex. However, the role of interhemispheric projections in shaping cortical responses to sound and frequency tuning in awake animals is unclear. Here we use translaminar single unit recordings and optogenetic approaches to probe how callosal inputs modulate spontaneous and tone-evoked activity in A1 of awake mice. Brief activation of callosal inputs drove either short-latency increases or decreases in firing of individual neurons. Across all cortical layers, the majority of responsive regular spiking (RS) cells received short-latency inhibition, whereas fast spiking (FS) cells were almost exclusively excited. Consistent with the callosal-evoked increases in FS cell activity in vivo, brain slice recordings confirmed that parvalbumin (PV)-expressing cells received stronger callosal input than pyramidal cells or other interneuron subtypes. Acute in vivo silencing of the contralateral cortex generally increased spontaneous firing across cortical layers and linearly transformed responses to pure tones via both divisive and additive operations. The net effect was a decrease in signal-to-noise ratio for evoked responses and a broadening of frequency tuning curves. Together, these results suggest that callosal input regulates both the salience and tuning sharpness of tone responses in A1 via PV cell-mediated feedforward inhibition.SignificanceWe use in vitro intracellular and in vivo extracellular recordings to show how interhemispheric projections modulate sensory representations in primary auditory cortex. Callosal projections make preferential input onto parvalbumin-expressing interneurons, particularly to those in deeper layers. Silencing the contralateral cortex increased principal neuron spontaneous activity and broadened frequency tuning. These results indicate that the primary effect of the interhemispheric projection is to sharpen frequency tuning and enforce the signal to noise ratio.}, URL = {https://www.eneuro.org/content/early/2020/08/05/ENEURO.0256-20.2020}, eprint = {https://www.eneuro.org/content/early/2020/08/05/ENEURO.0256-20.2020.full.pdf}, journal = {eNeuro} }