Learning and Memory NeuroReport 0959-4965 # Lippincott Williams & Wilkins Acute stress and re-exposure to the stressful context suppress spontaneous unit activity in the basolateral amygdala via NMDA receptor activation Tracey J. Shors Department of Psychology and Center for Neuroscience, 152 Frelinghuysen Road, Rutgers University, Piscataway, NJ 08903, USA EXPOSURE to an acute stressor of intermittent tail- shocks enhances acquisition of the classically condi- tioned eyeblink response and the enhancement is dependent on NMDA receptor activation in the baso- lateral nucleus of the amygdala. In the present study, multiple units (spikes/s) were recorded from the baso- lateral amygdala in response to the stressor of inter- mittent tailshocks (thirty, 1 mA, 1s, 1/min) and upon re-exposure to the context in which the stress was administered. Exposure to the stressor suppressed mul- tiple unit activity in the basolateral/lateral amygdala (67% of baseline) which, in some cases, persisted for 48 h after stressor cessation. Re-exposure to the stressful context reactivated the suppression in unit activity (69% of baseline). In a second experiment, it was determined that the stress-induced suppression of neu- ronal activity was prevented by NMDA receptor antag- onism during stressor exposure. It is proposed that the stress-induced suppression of background unit activity enhances the neural representation of environmental cues by enhancing their signal/background noise ratio and thereby facilitates the formation of associations between those cues. NeuroReport 10:2811±2815 # 1999 Lippincott Williams & Wilkins. Key words: Associative learning; Basolateral; Classical conditioning; Fear; Glutamate Introduction Stressful and emotional events can affect the acquisi- tion of new memories. Speci®cally, male rats ex- posed to an aversive stressor learn to associate discrete pieces of information at a facilitated rate [1±5]. In these studies, training consisted of expo- sure to paired presentations of an auditory condi- tioned stimulus (CS) that was followed by and co- terminated with an unconditioned stimulus (US) of periorbital eyelid stimulation. After repeated pairing of the stimuli, rats learn to blink in response to the CS. Rats exposed to either intermittent tailshocks or swim stress acquire the conditioned response (CR) at facilitated rate relative to rats that are not stressed. The facilitation is induced within 1 h of stressor exposure and persists for > 24 h after stressor cessa- tion. Moreover, the facilitated acquisition can be reactivated days later by exposing the animal to the stressful context. It is generally accepted that acquisition and ex- pression of the conditioned eyeblink response is dependent on deep nuclei of the cerebellum [6,7], but the facilitation of the CR by stress is dependent on additional brain structures such as the amygdala. We have reported that injection of the NMDA antagonist AP5 into the basolateral/lateral nucleus of the amygdala before stressor exposure prevents the facilitated acquisition, whereas antagonism in the central nucleus of the amygdala has no effect [2]. In addition, exposure to the stressor, as well as re- exposure to the stressful context, enhances [ 3 H]PDBu binding, a marker for protein kinase C, in the basolateral nucleus. The enhancement in [ 3 H]PDBu binding was similarly prevented by NMDA receptor antagonism during the stressful event [8]. In combination, these studies suggest that NMDA receptor activation in the basolateral nu- cleus is playing a critical role in the stress-induced facilitation of associative learning in the male rat. The mechanism mediating the expression of the facilitation is unknown, but presumably includes electrophysiological changes in the amygdala during and after stressor exposure. In the present experi- ments, we measured the effects of the stressor on spontaneous unit activity in the basolateral nucleus. After establishing that exposure to the stressor suppressed unit activity and the effect was persis- tent, we tested whether the effect could be reacti- vated by re-exposing the rat to the stressful context days after stressor cessation. Finally, we determined whether the effect of stress on unit activity was NeuroReport 10, 2811±2815 (1999) Vol 10 No 13 9 September 1999 2811