Optogenetic control of excitatory synapses in the accumbens during behavior

描述（由申请人提供）：了解奖励相关行为背后的神经回路对于开发精确有效的成瘾行为治疗方法至关重要。虽然许多大脑区域对奖励相关行为的表现和表达都很重要，但伏隔核（NAc）被认为是将生物体的情感状态转化为运动动作的关键脑核。因为NAc是异质的；由于大脑接收来自基底外侧杏仁核（BLA）和内侧前额叶皮层（mPFC）等区域的多种谷氨酸能输入以及来自腹侧被盖区的多巴胺能输入，因此很难研究特定突触连接在控制行为中的作用。为了避免这种情况，我们建议使用光遗传刺激通道视紫红质-2 （ChR2）来特异性控制从BLA和mPFC到NAc的神经传递。我们将首先选择性地将ChR2引入BLA和mPFC的谷氨酸能神经元，并通过光学刺激表征它们的放电特性。在NAc中特定谷氨酸末端亚群中表达ChR2后，我们将通过检查突触强度和谷氨酸释放概率来表征传入特异性神经传递。最后，我们将分析光刺激BLA或mPFC对NAc突触是否可以增强行为反应，从而促进目标导向行为。这些实验可以提供关于特定兴奋性输入NAc维持强化的能力的重要和新颖的信息，同时也定义了神经回路中可以驱动奖励相关行为的最小单元。

DESCRIPTION (provided by applicant): Understanding the neural circuitry that underlies reward-related behavior is essential for developing precise and effective treatments for addictive behavior. While many brain regions are important for the manifestation and expression of reward-related behavior, the nucleus accumbens (NAc) is thought to be a brain nucleus critical for translating the affective state of an organism into a motor action. Because the NAc is heterogeneous; receiving diverse glutamatergic inputs from areas such as the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) as well as dopaminergic input from the ventral tegmental area, it has been difficult to study the contribution of a specific synaptic connections in controlling behavior. To circumvent this, we propose here to use optogenetic stimulation of channelrhodopsin-2 (ChR2) to specifically control neural transmission from the BLA and mPFC to the NAc. We will first selectively introduce ChR2 into glutamatergic neurons of the BLA and mPFC and characterize their firing properties with optical stimulation. Following expression of ChR2 in specific subsets of glutamate terminals in the NAc, we will characterize afferent-specific neurotransmission by examine synaptic strength and glutamate release probability. Finally, We will assay whether optical stimulation of BLA or mPFC to NAc synapses can reinforce behavioral responding, thus promoting goal-directed behavior. These experiments could provide important and novel information about the ability of particular excitatory inputs into the NAc to sustain reinforcement while also defining a minimal unit within a neural circuit that can drive reward-related behavior.