| A ROLE FOR NEURONAL NITRIC OXIDE SYNTHASE (nNOS) IN
AUDITORY PAVLOVIAN FEAR CONDITIONING |
| G.E. Schafe*; S.M. Rodrigues; A.M. Schoute; J.E.
LeDoux |
| Ctr for Neural Sci, NYU, New York, NY, USA |
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Nitric oxide (NO) has been
widely implicated in synaptic plasticity and memory formation. In
studies of long-term potentiation (LTP), NO is thought to serve as
a  retrograde messenger that contributes to pre-synaptic
aspects of LTP expression. In this study, we examined the role of
the neuronal isoform of the enzyme responsible for generating NO,
neuronal nitric oxide synthase (nNOS), in Pavlovian fear conditioning.
We first evaluated the cellular localization of the active form of
the enzyme (pnNOS) in the lateral nucleus of the amygdala (LA), a
critical site of plasticity in fear conditioning. At the light microscopic
level, pnNOS-immunoreactivity appeared to be expressed throughout
the LA, and was expressed primarily in cytoplasm and proximal dendrites.
Next, we used Western immunoblotting to measure changes in pnNOS in
the LA after fear conditioning. Preliminary findings revealed a significant
increase in pnNOS levels in the LA of conditioned animals relative
to controls. This increase peaked at 3 hr following fear conditioning,
and was not accounted for by changes in total nNOS protein. Finally,
to evaluate the role of nNOS in fear conditioning, we gave rats pre-training
systemic injections of the selective nNOS antagonist, 7-nitroindazole
(7-NI; 30 mg/kg). Relative to vehicle controls, 7-NI produced a significant
disruption of long-term auditory fear conditioning (at 24 Hr). Short-term
memory (at 2 Hr) was left intact. Together, these findings suggest
that NO is an important component of memory formation of auditory
fear conditioning, possibly as a retrograde signal that participates
in presynaptic plasticity in the LA.
Supported by: MH38774, MH46516, & MH62519
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