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1.
Elife ; 102021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821218

RESUMO

Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a 1-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.


Assuntos
Prosencéfalo Basal/fisiologia , Neurônios Colinérgicos/fisiologia , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Camundongos/fisiologia , Animais , Feminino , Masculino , Reforço Psicológico
2.
Neuron ; 103(6): 1164-1177.e6, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31351757

RESUMO

Animals learn to fear conditioned sound stimuli (CSs) that accompany aversive unconditioned stimuli (USs). Auditory cortex (ACx) circuits reorganize to support auditory fear learning when CS-evoked activity temporally overlaps with US-evoked acetylcholine release from the basal forebrain. Here we describe robust fear learning and acetylcholine-dependent ACx plasticity even when the US is delayed by several seconds following CS offset. A 5-s CS-US gap was not bridged by persistent CS-evoked spiking throughout the trace period. Instead, within minutes following the start of conditioning, optogenetically identified basal forebrain neurons that encode the aversive US scaled up responses to the CS and increased functional coupling with the ACx. Over several days of conditioning, bulk imaging of cholinergic basal forebrain neurons revealed sustained sound-evoked activity that filled in the 5-s silent gap preceding the US. These findings identify a plasticity in the basal forebrain that supports learned associations between sensory stimuli and delayed reinforcement.


Assuntos
Acetilcolina/metabolismo , Córtex Auditivo/fisiologia , Prosencéfalo Basal/fisiologia , Neurônios Colinérgicos/fisiologia , Condicionamento Clássico/fisiologia , Medo , Reforço Psicológico , Estimulação Acústica , Animais , Prosencéfalo Basal/citologia , Prosencéfalo Basal/metabolismo , Neurônios Colinérgicos/metabolismo , Camundongos , Plasticidade Neuronal , Optogenética , Fatores de Tempo
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