CGRP inhibits neurons of the bed nucleus of the stria terminalis: implications for the regulation of fear and anxiety

J Neurosci. 2014 Jan 1;34(1):60-5. doi: 10.1523/JNEUROSCI.3473-13.2014.


The bed nucleus of the stria terminalis (BNST) is thought to generate anxiety-like states via its projections to autonomic and neuroendocrine regulatory structures of the brain. However, because most BNST cells are GABAergic, they are expected to inhibit target neurons. In contrast with this, infusion of calcitonin gene-related peptide (CGRP) into BNST was reported to potentiate anxiety while activating BNST targets. The present study aimed to shed light on this paradox. The CGRP innervation of BNST originates in the pontine parabrachial nucleus and targets its anterolateral sector (BNST-AL). Thus, we investigated the effects of CGRP on BNST-AL neurons using patch recordings in vitro in male rats. CGRP did not alter the passive properties of BNST-AL cells but increased the amplitude of IPSPs evoked by stimulation of the stria terminalis (ST). However, IPSP paired-pulse ratios were unchanged by CGRP, and there was no correlation between IPSP potentiation and variance, suggesting that CGRP acts postsynaptically. Consistent with this, CGRP hyperpolarized the GABA-A reversal of BNST-AL cells. These results indicate that CGRP increases ST-evoked GABA-A IPSPs and hyperpolarizes their reversal potential through a postsynaptic change in Cl(-) homeostasis. Overall, our findings suggest that CGRP potentiates anxiety-like behaviors and increases neural activity in BNST targets, by inhibiting BNST-AL cells, supporting the conclusion that BNST-AL exerts anxiolytic effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / physiopathology*
  • Anxiety / psychology
  • Calcitonin Gene-Related Peptide / toxicity*
  • Fear / drug effects
  • Fear / physiology*
  • Fear / psychology
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Organ Culture Techniques
  • Rats
  • Rats, Inbred Lew
  • Septal Nuclei / drug effects
  • Septal Nuclei / physiology*


  • Calcitonin Gene-Related Peptide