Previous Stress Facilitates Fear Memory, Attenuates GABAergic Inhibition, and Increases Synaptic Plasticity in the Rat Basolateral Amygdala

Abstract

In experiments designed to investigate the relationship between stress and the acquisition of new fear memories, it was found that previous exposure to a restraint session increased fear conditioning in a contextual fear paradigm. Moreover, the infusion of bicuculline, a competitive antagonist of GABA A receptors, into the basolateral amygdala complex (BLA), but not into the central amygdaloid nucleus, induced the same behavioral effect. Pretreatment with midazolam (MDZ), a positive modulator of GABA A sites, prevented the facilitating influence on fear memory of both stress and GABA A receptor blockade in the BLA. These data suggest that facilitation of fear conditioning could be causally related to increased neuronal excitability attributable to depressed GABAergic inhibition in the BLA. To test this hypothesis, evoked potentials were studied in brain slices from stressed animals. Potentials evoked in the BLA by single stimuli applied to the external capsule showed multispike responses, suggestive of GABAergic disinhibition. These multiple responses were no longer evident after the slices were perfused with diazepam or if the stressed animals were pretreated with MDZ. In slices from stressed rats, paired-pulse inhibition (GABA dependent) was suppressed. Also, in stressed animals, long-term potentiation (LTP) was induced with a single train of high-frequency stimulation, which did not induce LTP in control rats. Moreover, MDZ pretreatment prevented the facilitating influence of stress on LTP induction. All of these findings support the hypothesis that previous stress attenuates inhibitory GABAergic control in the BLA, leading to neuronal hyperexcitability and increased plasticity that facilitates fear learning.

Prefrontal/Amygdalar System Determines Stress Coping Behavior Through 5-HT/GABA Connection

“…It was first demonstrated that, in mice, a stressful experience such as restraint induces a time-dependent increase of 5-HT output in the mpFC and of GABA in the BLA, in agreement with previous reports (Reznikov et al, 2009;Pascucci et al, 2009), and that selective depletion of cortical 5-HT canceled out these stress-induced responses, thus pointing to a controlling role of GABAergic transmission in amygdala by prefrontal 5-HT during stress. Electrophysiological studies indicated that previous stress and repeated administration of corticotrophin-releasing factor receptor agonist into the BLA reduces GABAergic neurotransmission in this structure, and this impairment is involved in the enhancement of conditioned fear behavior and anxiety (Rodríguez Manzanares et al, 2005;Rainnie et al, 2004). These results seems contrasting with ours showing that acute stress increases GABA release in BLA and that bilateral L-allylglycine infusion into the BLA reduces immobility during FST.…”

Previous Stress Attenuates the Susceptibility to Midazolam's Disruptive Effect on Fear Memory Reconsolidation: Influence of Pre-Reactivation D-Cycloserine Administration

“…There is evidence that earlier experience with aversive events facilitate the formation of new fear memories in classic fear learning paradigms (Cordero et al, 2003;Rodríguez Manzanares et al, 2005;Shors, 2001). Our findings showed comparable amounts of freezing between control and stressed animals during the reactivation session (3 or 5 min), regardless of memory age.…”

“…On day 1, rats were placed for 30 min in the plastic restrainer. This procedure was selected on the basis of earlier findings from our laboratory using a similar stress protocol to that performed in this study (Martijena et al, 1997(Martijena et al, , 2002Rodríguez Manzanares et al, 2005;Isoardi et al, 2007). In these studies we showed that stress exposure attenuated the inhibitory GABAergic control in BLA, leading to neuronal hyperexcitability and facilitated induction of LTP in BLA, associated with the enhancement of fear memory.…”

“…In line with this argument, it has been proposed that the decrease in the inhibitory GABAergic control has a major role in the promoting effect of stress on both formation of fear memory and induction of long-term potentiation (LTP) in the basolateral amygdala complex (BLA) (Rodríguez Manzanares et al, 2005). Moreover, not only allosteric modulators of GABA-A receptors such as benzodiazepine (BDZ) agents (positive modulators) but also the inverse agonist (negative modulators) of BDZ sites have a decisive influence on learning and memory processes (Bovet et al, 1966;Brioni and McGaugh, 1988;Brioni et al, 1993;Chapouthier and Venault, 2002;Izquierdo et al, 1990;Jasnow and Huhman, 2001;Luft et al, 2004).…”

“…Although these effects are dependent on a number of factors (Bisaz et al, 2008), numerous studies have revealed a facilitating role of stress, and of hormones functionally associated with stressful experiences on the consolidation of aversive memory (Cordero et al, 2003;McGaugh, 2002;Rodríguez Manzanares et al, 2005;Roozendaal et al, 2008;Shors and Mathew, 1998). These results are consistent with the widespread notion that emotionally arousing experiences induce stronger and long-lasting memories than neutral ones (Cahill and McGaugh, 1998;McGaugh, 2004;Sandi, 1998).…”