SOMATOSENSORY CORTICAL HISTAMINE DYNAMICS TRACK TASK CONTEXT AND SHAPE PV ENSEMBLE ACTIVITY

Arousal and behavioral drive modulate sensory processing by shifting cortical networks into distinct states. The histaminergic tuberomammillary nucleus (TMN) is recruited during motivated arousal and projects throughout the brain, yet how histamine shapes cortical circuit dynamics is poorly understood. Cortical parvalbumin-positive (PV) interneurons regulate attention and sensory processing and are excited by histamine. We asked how motivated behavior influences cortical histamine tone, and how histamine tone modulates PV ensembles. We first performed 2-photon (2P) imaging of primary somatosensory cortex (SI) histamine tone with the GRAB-HA sensor in a somatosensory stimulus-reward task across days. Histamine tone rapidly increased during behavior. Further, during initial sessions, histamine tone was stable during a 30-minute pre-task baseline, but in later sessions rose rapidly upon entry to the task context (N=2 mice). In parallel, TMN-to-SI axon calcium imaging during task context revealed heterogeneous axonal response profiles (preliminary; N=4 mice). Subsequently, we enhanced histaminergic signaling with the H3 receptor inverse agonist ciproxifan, and quantified PV ensemble activity using both 2P PV calcium imaging and PV voltage imaging in layer 2/3 of awake mice. Calcium imaging revealed reduced PV noise correlations pre-stimulus (decorrelation), and larger stimulus-evoked responses after drug delivery (N=3 mice). PV voltage imaging during vibrissae stimulation showed increased stimulus-evoked gamma power and spiking after drug delivery (N=4 mice). Together, these results suggest that context-associated histamine recruitment biases SI toward an engaged inhibitory state, characterized by reduced baseline PV ensemble variability and enhanced PV sensory-evoked and gamma responses.