Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience.

Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system, yet their exact role in awake behaviors remains unclear. We performed bulk calcium measurements and electrophysiology with optogenetic tagging from the horizontal limb of the diagonal band of Broca (HDB) while male mice were performing an associative learning task. BFPVNs responded with a distinctive, phasic activation to punishment, but showed slower and delayed responses to reward and outcome-predicting stimuli. Optogenetic inhibition during punishment impaired the formation of cue-outcome associations, suggesting a causal role of BFPVNs in associative learning. BFPVNs received strong inputs from the hypothalamus, the septal complex and the median raphe region, while they synapsed on diverse cell types in key limbic structures, where they broadcasted information about aversive stimuli. We propose that the arousing effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions.

Training protocol for probabilistic Pavlovian conditioning in mice using an open-source head-fixed setup.

High throughput, temporally controlled, reproducible quantitative behavioral assays are important for understanding the neural mechanisms underlying behavior. Here, we provide a step-by-step training protocol for a probabilistic Pavlovian conditioning task, where two auditory cues predict probabilistic outcomes with different contingencies. This protocol allows us to study the differential behavioral and neuronal correlates of expected and surprising outcomes. It has been tested in combination with chronic in vivo electrophysiological recordings and optogenetic manipulations in ChAT-Cre and PV-Cre mouse lines. For complete details on the use and execution of this protocol, please refer to Hegedüs et al. (2021).