Pakan, J. | Search bioRxiv

bioRxiv2026

Distinct regulation of intrinsic persistent firing by cholinergic, noradrenergic and dopaminergic neuromodulations in the mouse auditory cortex

Neuromodulators shape brain function by regulating neural activity in area- and state-dependent manners. While persistent firing (PF), a cellular correlate of short-term information retention, is strongly regulated by neuromodulation in executive and memory areas, such regulation in the sensory cortex remains less well understood. Here, using in vitro patch-clamp recordings, we investigated how cholinergic, noradrenergic, and dopaminergic systems regulate intrinsic PF in mouse auditory cortex (AC) neurons. We found that cholinergic and noradrenergic activation support PF, similar to observations in the prefrontal cortex (PFC) but unlike noradrenergic suppression seen in the hippocampus. In contrast, dopamine and D1 receptor activation showed no clear effect on AC PF, contrasting with their suppressive role in the PFC. Furthermore, PF was significantly stronger in corticocollicular than corticocallosal neurons. These findings reveal diverse monoamine regulation of intrinsic PF, offering a potential cellular basis for sensory information maintenance under conditions of stress and reward.

neuroscience↗

bioRxiv2019

Cerebellar-recipient motor thalamus drives behavioral context-specific movement initiation

To initiate goal-directed behavior, animals must transform sensory cues into motor commands that generate appropriately timed actions. Sensorimotor transformations along the cerebellar-thalamocortical pathway are thought to shape motor cortical output and movement timing, but whether this pathway initiates goal-directed movement remains poorly understood. Here, we recorded and perturbed activity in cerebellar-recipient regions of motor thalamus (dentate / interpositus nucleus-recipient regions, MThDN/IPN) and primary motor cortex (M1) in mice trained to execute a cued forelimb lever push task for reward. MThDN/IPN population responses were dominated by a time-locked increase in activity immediately prior to movement that was temporally uncoupled from cue presentation, providing a fixed latency feedforward motor timing signal to M1FL. Blocking MThDN/IPN output suppressed cued movement initiation. Stimulating the MThDN/IPN thalamocortical pathway in the absence of the cue recapitulated cue-evoked M1 membrane potential dynamics and forelimb behavior in the learned behavioral context, but generated semi-random movements in an altered behavioral context. Thus, cerebellar-recipient motor thalamocortical input to M1 is indispensable for the generation of motor commands that initiate goal-directed movement, refining our understanding of how the cerebellar-thalamocortical pathway contributes to movement timing.

neuroscience↗