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The Journal of Neuroscience, November 15, 2001, 21(22):9009-9017
Consolidation of Extinction Learning Involves Transfer from
NMDA-Independent to NMDA-Dependent Memory
Edwin
Santini1,
Robert
U.
Muller2, and
Gregory J.
Quirk1
1 Department of Physiology, Ponce School of Medicine,
Ponce, Puerto Rico, 00732, and 2 Department of Physiology,
State University of New York Health Science Center at Brooklyn,
Brooklyn, New York 11203
Extinction of conditioned fear to a tone paired with foot shock is
thought to involve the formation of new memory. In support of this,
previous studies have shown that extinction of conditioned fear depends
on NMDA receptor-mediated plasticity. To further investigate the
role of NMDA receptors in extinction, we examined the effects of the
NMDA antagonist
D( )-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid
(CPP) on the extinction of conditioned freezing and suppression of bar
pressing (conditioned emotional response). Rats extinguished normally
during a 90 min session in the presence of systemic CPP (10 mg/kg), but
were unable to recall extinction learning 24 hr later. This suggests
that an NMDA-independent form of plasticity supports short-term
extinction memory, but NMDA receptors are required for consolidation
processes leading to long-term extinction memory. Surprisingly,
extinction learned in the presence of CPP was recalled normally when
tested 48 hr after training, suggesting a delayed consolidation process
that was able to improve memory in the absence of further training.
Delayed consolidation involves NMDA receptors because CPP injected on
the rest day between training and test prevented 48 hr recall of
extinction learned under CPP. Control experiments showed that the
effect of CPP on memory consolidation was not caused by state-dependent
learning or reduced expression of freezing under CPP. These findings
demonstrate that NMDA receptor activation is critical for consolidation
of extinction learning and that this process can be initiated after
training has taken place. We suggest that consolidation of extinction
involves off-line relearning that reinforces extinction memory through
NMDA-mediated plasticity, perhaps in prefrontal-amygdala circuits.
Key words:
fear conditioning; medial prefrontal cortex; amygdala; spontaneous recovery; LTP; infralimbic
Copyright © 2001 Society for Neuroscience 0270-6474/01/21229009-09$05.00/0
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