STIMULUS- AND STATE-DEPENDENT CONTROL OF LAYER 1 NDNF INTERNEURONS IN PRIMARY VISUAL CORTEX

Layer 1 interneurons (L1-INs) are strategically positioned to regulate the integration of bottom-up sensory drive and top-down signals, yet the rules governing their recruitment and contribution to cortical computation remain unclear. We focused on NDNF-expressing L1-INs in mouse primary visual cortex (V1) and asked how visual stimulus statistics and behavioral state shape their activity, and which cellular mechanisms govern their patterns. We combined in vivo two-photon calcium imaging in awake mice with genetic targeting and optogenetic manipulations. Across stimulus classes, static and drifting gratings elicited activation in only a small subset of NDNF-INs, whereas natural images recruited a larger proportion. This supports the idea that L1-IN recruitment is preferentially enhanced under conditions eliciting sparse visually evoked activity. Supporting this hypothesis, systematic contrast manipulations revealed strong stimulus dependence: low contrast preferentially recruited NDNF-INs, whereas higher contrast inhibited them. This contrast dependence was opposite to that observed in SST-interneurons, suggesting complementary stimulus regimes for these dendrite-targeting classes. Given the state dependence of NDNF-INs, we compared activity at rest and during locomotion. The fraction of excited versus inhibited cells during visual stimulation was similar across states, but locomotion produced a comparable gain increase across response types, indicating preserved stimulus selectivity with state-dependent amplification. Finally, in vitro intracellular recordings revealed that glutamatergic synapses onto NDNF-INs have a prominent NMDA receptor component, prolonging synaptic responses and expanding the temporal integration window. Ongoing work tests whether the slow integrative NDNF dynamics, together with SST-mediated inhibition, promote sparse visual representations to gate dendritic processing in L2/3 PNs.