Layer 1 NDNF interneurons modulate thalamocortical input to the auditory cortex

Neural microcircuits in the auditory cortex (AuC) are essential for auditory information processing. Recent studies identified the basal region of the ventromedial nucleus of the thalamus (bVM), which affects AuC neuronal responsiveness and contributes to sound discrimination. However, the microcircuit organization by which bVM influences AuC neuronal responsiveness remains unclear. Here, using anatomical tracing, slice electrophysiology, and optogenetics, we found that bVM formed monosynaptic connections with both neuron-derived neurotrophic factor-positive interneurons (NDNF-INs) in L1 and pyramidal neurons (PYRs) in L2/3, with polysynaptic engagement of other L2/3 interneuron subtypes. Notably, NDNF-INs selectively regulated bVM-driven inputs to parvalbumin-expressing interneurons (PV-INs), but not to vasoactive intestinal peptide-expressing interneurons (VIP-INs) or somatostatin-expressing interneurons (SST-INs), forming a possible cell-specific disinhibitory circuit in AuC L2/3 circuits. These findings define a circuit diagram of the bVM → AuC pathway and establish NDNF-INs as a key regulator of thalamocortical information flow.