| First Author | Laing BT | Year | 2023 |
| Journal | Curr Biol | Volume | 33 |
| Issue | 15 | Pages | 3215-3228.e7 |
| PubMed ID | 37490921 | Mgi Jnum | J:339331 |
| Mgi Id | MGI:7519898 | Doi | 10.1016/j.cub.2023.06.070 |
| Citation | Laing BT, et al. (2023) Anterior hypothalamic parvalbumin neurons are glutamatergic and promote escape behavior. Curr Biol 33(15):3215-3228.e7 |
| abstractText | The anterior hypothalamic area (AHA) is a critical structure for defensive responding. Here, we identified a cluster of parvalbumin-expressing neurons in the AHA (AHA(PV)) that are glutamatergic with fast-spiking properties and send axonal projections to the dorsal premammillary nucleus (PMD). Using in vivo functional imaging, optogenetics, and behavioral assays, we determined the role of these AHA(PV) neurons in regulating behaviors essential for survival. We observed that AHA(PV) neuronal activity significantly increases when mice are exposed to a predator, and in a real-time place preference assay, we found that AHA(PV) neuron photoactivation is aversive. Moreover, activation of both AHA(PV) neurons and the AHA(PV) --> PMD pathway triggers escape responding during a predator-looming test. Furthermore, escape responding is impaired after AHA(PV) neuron ablation, and anxiety-like behavior as measured by the open field and elevated plus maze assays does not seem to be affected by AHA(PV) neuron ablation. Finally, whole-brain metabolic mapping using positron emission tomography combined with AHA(PV) neuron photoactivation revealed discrete activation of downstream areas involved in arousal, affective, and defensive behaviors including the amygdala and the substantia nigra. Our results indicate that AHA(PV) neurons are a functional glutamatergic circuit element mediating defensive behaviors, thus expanding the identity of genetically defined neurons orchestrating fight-or-flight responses. Together, our work will serve as a foundation for understanding neuropsychiatric disorders triggered by escape such as post-traumatic stress disorder (PTSD). |
