Abstract
A variety of inhibitory pathways encompassing different interneuron types shape activity of neocortical pyramidal neurons. While basket cells (BCs) mediate fast lateral inhibition between pyramidal neurons, Somatostatin-positive Martinotti cells (MCs) mediate a delayed form of lateral inhibition. Neocortical circuits are under control of acetylcholine, which is crucial for cortical function and cognition. Acetylcholine modulates MC firing, however, precisely how cholinergic inputs affect cortical lateral inhibition is not known. Here, we find that cholinergic inputs selectively augment and speed up lateral inhibition between pyramidal neurons mediated by MCs, but not by BCs. Optogenetically activated cholinergic inputs depolarize MCs through activation of ß2 subunit-containing nicotinic AChRs, not muscarinic AChRs, without affecting glutamatergic inputs to MCs. We find that these mechanisms are conserved in human neocortex. Cholinergic inputs thus enable cortical pyramidal neurons to recruit more MCs, and can thereby dynamically highlight specific circuit motifs, favoring MC-mediated pathways over BC-mediated pathways.
Highlights
A variety of inhibitory pathways encompassing different interneuron types shape activity of neocortical pyramidal neurons
As the majority of interneurons in the cortex express acetylcholine receptors (AChRs)[9,11,20,21,22,23], we tested whether acetylcholinergic (ACh) inputs that come mainly from the basal forebrain (BF) modulate disynaptic lateral inhibition between pyramidal neurons
We find that (1) in layer 2/3 (L2/3) and L5, optogenetic activation of mainly BF projections shortens the delay time and increases the duration of delayed lateral inhibition via Martinotti cells of neighboring pyramidal neurons, while fast lateral inhibition is not affected by cholinergic inputs
Summary
A variety of inhibitory pathways encompassing different interneuron types shape activity of neocortical pyramidal neurons. While basket cells (BCs) mediate fast lateral inhibition between pyramidal neurons, Somatostatin-positive Martinotti cells (MCs) mediate a delayed form of lateral inhibition. Lateral inhibition, a form of feedback inhibition generated by activity in local circuits of pyramidal neurons and interneurons, can be mediated by parvalbumin (PV)-positive fast-spiking basket cells as well as somatostatin (SOM)-positive interneurons[3,4,5]. How cholinergic inputs affect lateral inhibition is not known It is not known whether lateral inhibition between pyramidal neurons exists in human neocortical circuits. In simultaneous recordings from synaptically connected neocortical neurons we find that only delayed lateral inhibition via MCs is modulated by cholinergic inputs, while fast lateral inhibition via BCs is not. We show that lateral inhibition is evolutionary conserved in the human neocortex and is facilitated by ACh through similar mechanisms
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