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Brief sounds produce a period of suppressed responsiveness in the auditory cortex (ACx). This forward suppression can last for hundreds of milliseconds and might contribute to mechanisms of temporal separation of sounds and stimulus-specific adaptation. However, the mechanisms of forward suppression remain unknown. We used in vivo recordings of sound-evoked responses in the mouse ACx and whole-cell recordings, two-photon calcium imaging in presynaptic terminals, and two-photon glutamate uncaging in dendritic spines performed in brain slices to show that synaptic depression at thalamocortical (TC) projections contributes to forward suppression in the ACx. Paired-pulse synaptic depression at TC projections lasts for hundreds of milliseconds and is attributable to a switch between firing modes in thalamic neurons. Thalamic neurons respond to a brief depolarizing pulse with a burst of action potentials; however, within hundreds of milliseconds, the same pulse repeated again produces only a single action potential. This switch between firing modes depends on Ca(v)3.1 T-type calcium channels enriched in thalamic relay neurons. Pharmacologic inhibition or knockdown of Ca(v)3.1 T-type calcium channels in the auditory thalamus substantially reduces synaptic depression at TC projections and forward suppression in the ACx. These data suggest that Ca(v)3.1-dependent synaptic depression at TC projections contributes to mechanisms of forward suppression in the ACx.

the journal of neuroscience/the journal of neuroscience

Forward Suppression in the Auditory Cortex Is Caused by the Ca<sub>v</sub>3.1 Calcium Channel-Mediated Switch from Bursting to Tonic Firing at Thalamocortical Projections

Forward Suppression in the Auditory Cortex Is Caused by the Cav3.1 Calcium Channel-Mediated Switch from Bursting to Tonic Firing at Thalamocortical Projections

Forward Suppression in the Auditory Cortex Is Caused by the Ca_v3.1 Calcium Channel-Mediated Switch from Bursting to Tonic Firing at Thalamocortical Projections