Distinct synchronization, cortical coupling and behavioural function of two basal forebrain cholinergic neuron types

Basal forebrain cholinergic neurons (BFCN) densely innervate the forebrain and modulate synaptic plasticity, cortical processing, brain states and oscillations. However, little is known about the functional diversity of cholinergic neurons and whether distinct types support different functions. To examine this question we recorded BFCN in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCN that markedly differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (BFCNBURST) fired in zero-lag synchrony with each other, phase-locked to cortical theta activity and fired precisely timed bursts of action potentials after reward and punishment. Regular firing cholinergic neurons (BFCNREG) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity (5-10 Hz), fired asynchronously with each other and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of BFCNBURST neurons to auditory cortex predicted the timing of mouse responses, whereas tone-evoked cortical coupling of BFCNREG predicted correct detections. We propose that cortical activation relevant for behavior is controlled by the balance of two cholinergic cell types, where the precise proportion of the strongly activating BFCNBURST follows an anatomical gradient along the antero-posterior axis of the basal forebrain.