Cell Reports (Oct 2019)

Dissecting the Roles of GABA and Neuropeptides from Rat Central Amygdala CRF Neurons in Anxiety and Fear Learning

  • Matthew B. Pomrenze,
  • Simone M. Giovanetti,
  • Rajani Maiya,
  • Adam G. Gordon,
  • Lauren J. Kreeger,
  • Robert O. Messing

DOI
https://doi.org/10.1016/j.celrep.2019.08.083
Journal volume & issue
Vol. 29, no. 1
pp. 13 – 21.e4

Abstract

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Summary: Central amygdala (CeA) neurons that produce corticotropin-releasing factor (CRF) regulate anxiety and fear learning. These CeACRF neurons release GABA and several neuropeptides predicted to play important yet opposing roles in these behaviors. We dissected the relative roles of GABA, CRF, dynorphin, and neurotensin in CeACRF neurons in anxiety and fear learning by disrupting their expression using RNAi in male rats. GABA, but not CRF, dynorphin, or neurotensin, regulates baseline anxiety-like behavior. In contrast, chemogenetic stimulation of CeACRF neurons evokes anxiety-like behavior dependent on CRF and dynorphin, but not neurotensin. Finally, knockdown of CRF and dynorphin impairs fear learning, whereas knockdown of neurotensin enhances it. Our results demonstrate distinct behavioral roles for GABA, CRF, dynorphin, and neurotensin in a subpopulation of CeA neurons. These results highlight the importance of considering the repertoire of signaling molecules released from a given neuronal population when studying the circuit basis of behavior. : Pomrenze et al. demonstrate that CRF neurons of the central amygdala differentially regulate fear and anxiety through the release of GABA and different neuropeptides. Keywords: corticotropin releasing factor, gamma-aminobutyric acid, dynorphin, neurotensin, fear, anxiety, amygdala, RNA interference