Chemogenetics enables manipulation of neuronal activity in experimental animals. While providing information about the transduced neuron expressing a ligand-activated molecule, chemogenetics does not provide understanding about the antecedent circuit that drives that neuron’s activity. For current approaches, this is not feasible, because the activating molecules are not genetically encoded. The insect allatostatin/allatostatin receptor system, a highly specific, powerful inhibitory chemogenetic approach, has this advantage, because the ligand, being a peptide, is genetically encoded. We developed viral vector-based systems to express biologically active allatostatin in neurons in vivo and allatostatin receptors in subpopulations of postsynaptic neurons. We demonstrate that activity-dependent release of allatostatin induces inhibition of allatostatin receptor-expressing neurons. We validate the approach in the vagal viscerosensory system where inhibitory, rather than the usual excitatory, viscerosensory input leads to sustained decreases in baroreceptor reflex sensitivity and bodyweight.

化学遗传学使得能够控制实验动物的神经元活性。在提供有关表达表达配体激活分子的转导神经元的信息时，化学遗传学并未提供对驱动该神经元活性的前回路的理解。对于当前的方法，这是不可行的，因为活化分子不是遗传编码的。昆虫的Allatostatin / Allatostatin受体系统是一种高度特异性，功能强大的抑制化学发生方法，具有此优势，因为作为肽的配体是经过基因编码的。我们开发了基于病毒载体的系统来在体内神经元中表达具有生物活性的阿托伐他汀和突触后神经元亚群中的阿托伐他汀受体。我们证明了活动依赖性释放的allatostatin诱导抑制allatostatin受体表达的神经元。我们在迷走神经内脏感觉系统中验证了这种方法，该方法是抑制性而不是通常的兴奋性内脏感觉输入会导致压力感受器反射敏感性和体重持续下降。