| Program#/Poster#: |
614.14/WW67 |
| Title: |
A role for orexins in fear learning
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| Location: |
Hall A-C |
| Presentation Time: |
Tuesday, Nov 15, 2011, 9:00 AM -10:00
AM |
| Authors: |
*R. M. SEARS1, J.
E. LEDOUX1,2;
1Ctr. for Neural Sci., New York Univ., New York, NY; 2Nathan
S. Kline Inst. for Psychiatric Res., Orangeburg, NY |
| Abstract: |
Anxiety and fear disorders involve
alterations of fear, due in part to persistent changes in fear processing
circuits in the brain. The current work seeks to demonstrate an unexplored
interaction between the hypothalamic orexin system and brain regions that
are critical for emotional learning. There is strong evidence that orexins
mediate stress and arousal responses to aversive stimuli. Such responses
may be required for the formation of fear memories. Preliminary data suggest
that central (ICV) administration of the orexin type 1 receptor (OrxR1)
antagonist SB 334867 prior to training impairs fear learning. A well-established
brain area for the formation, storage and retrieval of fear memories, and
the first logical target for orexin activity in fear, is the lateral nucleus
of the amygdala (LA). However, consistent with low receptor expression in
this area, we find that direct administration of SB 334867 in LA does not
affect fear learning. On the other hand, the locus coeruleus (LC), a major
source of brain norepinephrine, is known to receive dense projections from
orexin neurons, expresses high levels of OrxR1, and LC neurons are excited
by orexins. Indeed, preliminary data suggest that direct LC administration
of SB 334867 impairs the acquisition of fear memories. Clinical evidence
suggests that people deficient in orexins show impairments in fear memory
formation. Dysregulation of the orexin system may explain susceptibility
to fear and anxiety disorders and provide both a diagnostic measure and
treatment target for these disorders. |
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