Second-order fear conditioning prevented by blocking NMDA receptors in amygdala.
Antagonists of NMDA (N-methyl-D-aspartate)-type glutamate receptors disrupt several forms of learning. Although this might indicate that NMDA-receptor-mediated processes are critical for synaptic plasticity, there may be other mechanisms by which NMDA-receptor antagonism could interfere with learning. For instance, fear conditioning would be blocked by microinfusion of the NMDA-receptor antagonist AP5 (D,L-2-amino-5-phosphonovalerate) into the basolateral amygdala if AP5 inhibited routine synaptic transmission, thereby reducing the ability of stimuli to activate amygdala neurons. In second-order fear conditioning, the reinforcer is a fear-eliciting conditioned stimulus rather than an unconditioned stimulus. Expression of conditioned fear is amygdala-dependent and so provides a behavioural assessment of the ability of the reinforcer to activate amygdala neurons in the presence of AP5. We report here that intra-amygdala AP5 actually enhances expression of conditioned fear to the conditioned stimulus that provides the reinforcement signal for second-order conditioning. Nevertheless, acquisition of second-order fear conditioning is completely blocked. Our findings strongly support the view that NMDA receptors are critically involved in synaptic plasticity.
Gewirtz
J C
JC
Department of Psychology, Yale University, Ribicoff Research Facilities of the Connecticut Mental Health Center, New Haven 06508, USA. jonathan.gewirtz@yale.edu
Davis
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013216:Reflex, Startle
D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate