LeDoux Lab 2015 SfN Abstracts
 
Program#/Poster#: 254.13/W13
Title: The role of norepinephrine in the expression of Pavlovian defensive reactions
Location: Hall A
Presentation Time: Sunday, Oct 18, 2015, 1:00 PM - 5:00 PM
Presenter at Poster Sun, Oct. 18, 2015, 1:00 PM - 2:00 PM
Topics: ++F.02.cc. Fear and aversive learning and memory: Amygdala and extended amygdala circuits
Authors: *Y. GU1, R. M. SEARS1,2, E. M. VAZEY3, G. S. ASTON-JONES3, J. E. LEDOUX1,2;
1Ctr. for Neural Sci., New York Univ., New York, NY; 2Emotional Brain Inst., Nathan Kline Inst., Orangeburg, NY; 3Dept. of Neurosciences, Med. Univ. of South Carolina, Charleston, SC
Abstract: The modulatory role of norepinephrine (NE) in the amygdala, specifically the lateral nucleus of the amygdala (LA), has been studied in great detail using aversive Pavlovian paradigms. However, the central nucleus of the amygdala (CeA) also receives dense noradrenergic innervation, the function of which is not well understood. The CeA is the major output nucleus of the amygdala and is responsible for defensive responses to aversive stimuli. We therefore hypothesized that NE acting in CeA modules the expression of defensive reactions. Here, we used a combination of intracranial drug infusions and Designer Receptors Activated by Designer Drugs (DREADDs) to uncover the role of NE modulation of CeA functions in a Pavlovian threat conditioning paradigm. Decreased and increased expression of defensive responses were observed following direct CeA infusions of the β-receptor antagonist propranolol or the β-receptor agonist isoproterenol, respectively. Next we used viral vectors expressing DREADDs and engineered to specifically target norepinephrine-expressing neurons to study the role of the locus coeruleus (LC), a major source of norepinephrine release in the brain, in CeA-mediated defensive responses. Axon terminals in CeA were directly activated or inhibited using intra-CeA Clozapine-N-oxide (CNO) infusions before memory expression tests. Consistent with our pharmacology studies, we found that hM3Dq-mediated activation and hM4Di-mediated inhibition of LC terminals in CeA increased and decreased freezing behaviors, respectively. Taken together, these studies suggest that norepinephrine from LC activates β-receptors in CeA to positively modulate defensive responses to threatening stimuli.
Disclosures:  Y. Gu: None. R.M. Sears: None. E.M. Vazey: None. G.S. Aston-Jones: None. J.E. LeDoux: None.
Keyword (s): NOREPINEPHRINE
  AMYGDALA
  LOCUS COERULEUS
Support: MH038774
MH046516