Anterior hypothalamic parvalbumin neurons are glutamatergic and promote escape behavior

Featured Paper of the Month – January 2024

Published in Current Biology by Brenton Laing and Yeka Aponte, et al. of the NIDA IRP Neuronal Circuits and Behavior Section.

Summary

Using techniques including in vivo functional imaging, behavioral paradigms, and neuronal tracing, Laing et al. investigated a small population of parvalbumin neurons in the anterior hypothalamic area (AHA^PV). They demonstrated that AHA^PV neurons are glutamatergic and project to the premammillary dorsal nucleus (PMD). Additionally, they found that AHA^PV neuronal activity increases when mice are exposed to a predator and optogenetic activation of these neurons is aversive and evokes escape responding. Their study implicates AHA^PV neurons as a novel, genetically identified circuit element mediating fight-or-flight responses.

Publication Information

Laing, Brenton T; Anderson, Megan S; Bonaventura, Jordi; Jayan, Aishwarya; Sarsfield, Sarah; Gajendiran, Anjali; Michaelides, Michael; Aponte, Yeka

Anterior hypothalamic parvalbumin neurons are glutamatergic and promote escape behavior Journal Article

In: Curr Biol, vol. 33, no. 15, pp. 3215–3228.e7, 2023, ISSN: 1879-0445.

Abstract | Links

@article{pmid37490921b,

title = {Anterior hypothalamic parvalbumin neurons are glutamatergic and promote escape behavior},

author = {Brenton T Laing and Megan S Anderson and Jordi Bonaventura and Aishwarya Jayan and Sarah Sarsfield and Anjali Gajendiran and Michael Michaelides and Yeka Aponte},

url = {https://pubmed.ncbi.nlm.nih.gov/37490921/},

doi = {10.1016/j.cub.2023.06.070},

issn = {1879-0445},

year  = {2023},

date = {2023-08-01},

urldate = {2023-08-01},

journal = {Curr Biol},

volume = {33},

number = {15},

pages = {3215--3228.e7},

abstract = {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) 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 neurons in regulating behaviors essential for survival. We observed that AHA neuronal activity significantly increases when mice are exposed to a predator, and in a real-time place preference assay, we found that AHA neuron photoactivation is aversive. Moreover, activation of both AHA neurons and the AHA → PMD pathway triggers escape responding during a predator-looming test. Furthermore, escape responding is impaired after AHA 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 neuron ablation. Finally, whole-brain metabolic mapping using positron emission tomography combined with AHA 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 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).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}