Presynaptic control of top-down signaling in neocortical layer 1

The integration of bottom-up and top-down signals is crucial for perception and behavior. Neocortical layer 1 (L1) is a key target for top-down inputs and contains various GABAergic interneurons. Here, we investigated whether GABA can presynaptically regulate neurotransmitter release at top-down synapses targeting L1 of primary somatosensory cortex (S1). Our findings show that presynaptic GABA_B receptor activation suppresses corticocortical inputs from primary motor (M1) and secondary somatosensory cortices (S2) more than those from the posterior medial nucleus of the thalamus (POm). This effect varied by target cell type, with GABAergic interneurons being less affected. Finally, we demonstrate that L1 neuron-derived neurotrophic factor (NDNF)-expressing interneurons inhibit top-down synapses more effectively than somatostatin-expressing interneurons, and that POm drives L1 neurogliaform cells, a subtype of NDNF interneuron that elicits unitary GABA_B responses. These results reveal a novel circuit in which higher-order thalamus influences top-down corticocortical communication via L1 neurogliaform cells.