LeDoux Lab 2004 SfN Abstracts

BLOCKADE OF THE NR2B SUBUNIT OF THE NMDA RECEPTOR IMPAIRS FEAR EXTINCTION LEARNING
F.Sotres-Bayon*; D.E.A.Bush; J.E.LeDoux
Ctr. for Neural Sci., New York Univ, New York, NY, USA
NMDA receptors contribute to the synaptic plasticity that underlies learning and memory in a variety of brain systems. Fear conditioning, which is known to involve plasticity within the amygdala, depends on the NR2B subunit of the NMDA receptor. Additionally, the extinction of conditioned fear, which involves learning to inhibit the fear response, also appears to require NMDA-dependent plasticity in the amygdala. However, the specific role of the NR2B subunit in extinction learning has not yet been explored. Further, it is not known whether NMDA receptors are required for the initial learning of extinction (within-session extinction) as opposed to being involved in making this learning retrievable on a later occasion (between-session extinction). Rats that had previously undergone auditory fear conditioning (7 tone-footshock pairings) were pseudo-randomly allocated to one of two groups and injected systemically with vehicle or the NR2B antagonist, ifenprodil (5 mg/ml/kg, ip), 15 min prior to fear extinction training. Conditioned fear (freezing) to the tone was measured within the initial extinction training session (20 tone-alone presentations), and again 24 hr later (15 tone-alone presentations). Results showed that ifenprodil significantly impaired extinction learning on the first day of extinction (within-session), which was also associated with impaired extinction retrieval the next day (between-session). Thus, blockade of the NR2B subunit of the NMDA receptor impairs the acquisition of fear extinction. Results of previous studies suggesting a role of NMDA receptors in the retrieval of extinction may actually be due to this failure to acquire extinction. Studies are underway to identify the brain region(s) that may mediate these NR2B-dependent effects, with a focus on possible interactions between the amygdala and medial prefrontal cortex. Support Contributed By: R37 MH38774, P50 MH58911, K05 MH067048
Program No. 208.5 Poster presentation:Sunday, Oct. 24, 8:00 AM - 9:00 AM Location: NN20