Predator stress-induced crf release causes enduring sensitization of basolateral amygdala norepinephrine systems that promote ptsd-like startle abnormalities

Abha K. Rajbhandari, Brian A. Baldo, Vaishali P. Bakshi

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The neurobiology of post-traumatic stress disorder (PTSD) remains unclear. Intense stress promotes PTSD, which has been associated with exaggerated startle and deficient sensorimotor gating. Here, we examined the long-term sequelae of a rodent model of traumatic stress (repeated predator exposure) on amygdala systems that modulate startle and prepulse inhibition (PPI), an operational measure of sensorimotor gating. We show in rodents that repeated psychogenic stress (predator) induces long-lasting sensitization of basolateral amygdala (BLA) noradrenergic (NE) receptors (α1) via a corticotropin-releasing factor receptor 1 (CRF-R1)-dependent mechanism, and that these CRF1 and NE α1 receptors are highly colocalized on presumptive excitatory output projection neurons of the BLA. A profile identical to that seen with predator exposure was produced in nonstressed rats by intra-BLA infusions of CRF (200 ng/0.5μl), but not by repeated NE infusions (20μg/0.5μl). Infusions into the adjacent central nucleus of amygdala had no effect. Importantly, the predator stress- or CRF-induced sensitization of BLA manifested as heightened startle and PPI deficits in response to subsequent subthreshold NE system challenges (with intra-BLA infusions of 0.3 μg/0.5 μl NE), up to 1 month after stress. This profile of effects closely resembles aspects of PTSD. Hence, we reveal a discrete neural pathway mediating the enhancement ofNEsystem function seen in PTSD, and we offer a model for characterizing potential new treatments that may work by modulating this BLA circuitry.

Original languageEnglish
Pages (from-to)14270-14285
Number of pages16
JournalJournal of Neuroscience
Volume35
Issue number42
DOIs
StatePublished - 21 Oct 2015
Externally publishedYes

Keywords

  • Corticotropin-releasing factor
  • Corticotropin-releasing hormone
  • Noradrenergic
  • Prepulse inhibition
  • Schizophrenia
  • Sensorimotor gating

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