Probes for INS

Basolateral amygdala (BLA) principal cells are capable of driving and antagonizing behaviors of opposing valence. BLA neurons project to the central amygdala (CeA), which also participates in negative and positive behaviors. However, the CeA has primarily been studied as the site for negative behaviors, and the causal role for CeA circuits underlying appetitive behaviors is poorly understood. Here, we identify several genetically distinct populations of CeA neurons that mediate appetitive behaviors and dissect the BLA-to-CeA circuit for appetitive behaviors. Protein phosphatase 1 regulatory subunit 1B+ BLA pyramidal neurons to dopamine receptor 1+ CeA neurons define a pathway for promoting appetitive behaviors, while R-spondin 2+ BLA pyramidal neurons to dopamine receptor 2+ CeA neurons define a pathway for suppressing appetitive behaviors. These data reveal genetically defined neural circuits in the amygdala that promote and suppress appetitive behaviors analogous to the direct and indirect pathways of the basal ganglia.

To deconstruct the architecture and function of brain circuits, it is necessary to generate maps of neuronal connectivity and activity on a whole-brain scale. New methods now enable large-scale mapping of the mouse brain at cellular and subcellular resolution. We developed a framework to automatically annotate, analyze, visualize and easily share whole-brain data at cellular resolution, based on a scale-invariant, interactive mouse brain atlas. This framework enables connectivity and mapping projects in individual laboratories and across imaging platforms, as well as multiplexed quantitative information on the molecular identity of single neurons. As a proof of concept, we generated a comparative connectivity map of five major neuron types in the corticostriatal circuit, as well as an activity-based map to identify hubs mediating the behavioral effects of cocaine. Thus, this computational framework provides the necessary tools to generate brain maps that integrate data from connectivity, neuron identity and function.

Response to danger needs to be rapid and appropriate. In humans, nocifensive behaviors often precede conscious pain perception. Much is known about local spinal cord circuits for simple reflexive responses, but the mechanisms underlying more complex behaviors remain poorly understood. We now describe a brainstem circuit that controls escape responses to select noxious stimuli. Tracing experiments characterized a highly interconnected excitatory circuit involving the dorsal spinal cord, parabrachial nucleus (PBNl), and reticular formation (MdD). A combination of chemogenetic, optogenetic, and genetic ablation approaches revealed that PBNl Tac1 neurons are activated by noxious stimuli and trigger robust escape responses to heat through connections to the MdD. Remarkably, MdD Tac1 neurons receive excitatory input from the PBN and target both the spinal cord and PBN; activation of these neurons phenocopies the behavioral effects of PBNl Tac1neuron stimulation. These findings identify a substrate for controlling appropriate behavioral responses to painful stimuli.