Kimchi Eyal Y, Burgos-Robles Anthony, Matthews Gillian A, Chakoma Tatenda, Patarino Makenzie, Weddington Javier C, Siciliano Cody, Yang Wannan, Foutch Shaun, Simons Renee, Fong Ming-Fai, Jing Miao, Li Yulong, Polley Daniel B, Tye Kay M
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States.
Department of Neurology, Northwestern University, Chicago, United States.
Elife. 2024 Feb 20;12:RP89093. doi: 10.7554/eLife.89093.
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 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. 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 BLA 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.
基底前脑胆碱能神经元通过影响觉醒、注意力和记忆，调节生物体对环境刺激的处理和反应方式。然而，尚不清楚基底前脑胆碱能神经元是否直接参与条件行为，而不依赖于其在外部刺激处理中的次要作用。通过荧光成像，我们发现胆碱能神经元在对奖励的行为反应过程中是活跃的——甚至在奖励发放之前且在没有离散刺激的情况下也是如此。对基底前脑胆碱能神经元或其在基底外侧杏仁核（BLA）中的终末进行光刺激，选择性地促进了条件反应（舔舐），但不影响非条件行为或先天运动输出。胆碱能光刺激期间的体内电生理记录显示，BLA神经活动受到奖励依赖性抑制，但前额叶皮层不受影响。最后，体外实验表明，胆碱能终末的光刺激通过单突触毒蕈碱受体信号传导抑制BLA投射神经元活动，同时也促进BLA GABA能中间神经元的放电。综上所述，我们表明基底前脑胆碱能激活的神经和行为效应以靶标特异性方式受到奖励偶然性的调节。
