Cataldi Stefano, Lacefield Clay, Shashaank N, Sulzer David
Department of Psychiatry, Division of Molecular Therapeutics, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA.
Italian Academy, Columbia University, New York, NY 10027, USA.
Biomedicines. 2024 Dec 2;12(12):2755. doi: 10.3390/biomedicines12122755.
BACKGROUND/OBJECTIVES: Learning is classically modeled to consist of an acquisition period followed by a mastery period when the skill no longer requires conscious control and becomes automatic. Dopamine neurons projecting to the ventral striatum (VS) produce a teaching signal that shifts from responding to rewarding or aversive events to anticipating cues, thus facilitating learning. However, the role of the dopamine-receptive neurons in the ventral striatum, particularly in encoding decision-making processes, remains less understood.
Here, we introduce an operant conditioning paradigm using open-source microcontrollers to train mice in three sequential learning phases. employs classical conditioning, associating a 5 s sound cue (CS) with a sucrose-water reward. In , the CS is replaced by a lever press as the requirement for reward delivery, marking an operant conditioning stage. combines these elements, requiring mice to press the lever during the CS to obtain the reward. We recorded calcium signals from direct pathway spiny projection neurons (dSPNs) in the VS throughout the three phases of training.
We find that dSPNs are specifically engaged when the mouse makes a decision to perform a reward-seeking action in response to a CS but are largely inactive during actions taken outside the CS.
These findings suggest that direct pathway neurons in the VS contribute to decision-making in learned action-outcome associations, indicating a specialized role in initiating operant behaviors.
背景/目的：传统上认为学习由一个获取阶段和随后的掌握阶段组成，在掌握阶段技能不再需要有意识的控制并变得自动化。投射到腹侧纹状体（VS）的多巴胺神经元产生一种教学信号，该信号从对奖励或厌恶事件的反应转变为对线索的预期，从而促进学习。然而，腹侧纹状体中多巴胺受体神经元的作用，特别是在编码决策过程中的作用，仍不太清楚。
在这里，我们引入了一种使用开源微控制器的操作性条件反射范式，在三个连续的学习阶段训练小鼠。第一阶段采用经典条件反射，将5秒的声音线索（CS）与蔗糖水奖励联系起来。在第二阶段，CS被杠杆按压所取代，作为奖励发放的条件，标志着一个操作性条件反射阶段。第三阶段结合了这些元素，要求小鼠在CS期间按压杠杆以获得奖励。我们在整个训练的三个阶段记录了VS中直接通路棘状投射神经元（dSPN）的钙信号。
我们发现，当小鼠决定响应CS执行寻求奖励的行动时，dSPN会被特异性激活，但在CS之外的行动过程中基本不活跃。
这些发现表明，VS中的直接通路神经元有助于学习到的行动-结果关联中的决策，表明其在启动操作性行为中具有特殊作用。
