Reward contingency gates selective cholinergic suppression of amygdala neurons

Abstract

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward – even in prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex (PFC). Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic-receptor-signaling, while also facilitating firing in GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

Cell-type-specific striatal modulation of amygdalar acetylcholine in salience assignment

“…Consistent with prior observations 15,25 , we found that activation of the SI ChAT →BLA pathway did not induce any place preference (Figures S5G and S5H), or affect the movement (Figures S5I and S5J). In addition, activation of this pathway failed to support self-stimulation (Figures S5K-S5N).…”

“…Previous studies have shown that acetylcholine (ACh) is a key neuromodulator critical for conscious awareness, salience, and attentional control, and is essential for associative learning and memory [7][8][9][10][11][12][13][14][15]15,16,[16][17][18][19] . Cholinergic deficiencies represent a prominent feature of attention-related impairments observed in Alzheimer's disease and Parkinson's dementia 20,21 .…”

“…The principal neurons in the BLA have been shown to encode both positive and negative values of stimuli 32,34 . Recent studies have begun to reveal the essential role of BLA ACh in cue-reward learning, fear conditioning, and reinforcement prediction error 12,13,15,25,35 . However, the coding of various forms of behaviorally relevant salience in the BLA ACh has not been systematically investigated.…”