Optogenetic control of excitatory synapses in the accumbens during behavior

描述(由申请者提供)：了解与奖励相关的行为背后的神经回路对于开发准确有效的成瘾行为治疗方法至关重要。虽然大脑的许多区域对奖赏相关行为的表现和表达都很重要，但伏隔核(NAC)被认为是将有机体的情感状态转化为运动动作的关键脑核。由于NAC是异质性的，从基底外侧杏仁核(BLA)和内侧前额叶皮质(MPFC)等区域接收不同的谷氨酸能输入，以及从腹侧被盖区接收多巴胺能输入，因此很难研究特定突触联系在控制行为中的作用。为了避免这一点，我们建议使用光遗传刺激通道视紫红质-2(ChR2)来专门控制从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，并用光刺激来表征它们的放电特性。随着ChR2在NAC中谷氨酸终末的特定亚群中的表达，我们将通过检测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，我们将测试光刺激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到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与奖励相关的行为的最小单位。

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.