Amygdala Modulation Research Articles

Basolateral amygdala modulation of the nucleus accumbens dopamine response to stress: role of the medial prefrontal cortex.

The basolateral amygdala (BLA) is involved in modulating affective responses to stress and, along with the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), receives a stress-responsive dopamine (DA) projection from the ventral tegmental area. The present study was undertaken to characterize the role of BLA DA D1 and D2/D3 receptor subtypes in modulating the NAc and mPFC DA responses to stress. Voltammetry was used to monitor, in freely behaving rats, stress-induced DA release in NAc or mPFC after injection of D1 (SCH 23390) or D2/D3 (raclopride) receptor antagonist into BLA. Intra-BLA SCH 23390 injection potentiated stress-induced NAc DA release but attenuated the mPFC DA stress response; raclopride had no effect on either the NAc or mPFC DA responses to stress. Based on these results, we also examined the possibility that BLA can indirectly modulate the NAc DA stress response via its projection to mPFC. To do so we studied the effects of intra-mPFC co-administration of D1 (SKF 38393) and D2/D3 (quinpirole) receptor agonists on the potentiated NAc DA stress response resulting from intra-BLA SCH 23390 injection. Alone, mPFC D1 and D2/D3 receptor co-activation had no effect on stress-induced NAc DA release, but did prevent the potentiated NAc DA stress response produced by BLA D1 receptor blockade. These findings indicate that BLA DA modulates the NAc and mPFC DA stress responses via activation of the D1 receptor subtype. They also suggest that BLA DA modulates stress-induced NAc DA release indirectly by modulating the mPFC DA response to stress.

Affective analgesia following the administration of morphine into the amygdala of rats

The amygdala processes stimuli that threaten the individual and organizes the execution of affective behaviors that permit the individual to cope with the threat. The prototypical threat to an individual is exposure to a noxious stimulus. The present study evaluated the contribution of the amygdala in modulating the affective response of rats to noxious stimulation. Vocalization afterdischarges (VADs) are a validated model of the affective response of rats to noxious tailshock. The antinociceptive action of morphine microinjected into the amygdala on VAD thresholds was compared to its effect on the thresholds of other tailshock-elicited responses (vocalizations during shock, VDS and spinal motor reflexes, SMRs). Whereas VADs are organized within the forebrain, VDSs and SMRs are organized at medullary and spinal levels of the neuraxis, respectively. The bilateral administration of morphine into the basolateral complex of the amygdala (BLC) produced dose-dependent increases in VAD and VDS thresholds, although increases in VAD thresholds were significantly greater than increases in VDS thresholds. Administration of morphine into BLC was ineffective in elevating SMR thresholds. Morphine-induced increases in vocalization thresholds were reversed in a dose-dependent manner by microinjection of the opiate receptor antagonist methylnaloxonium into BLC. Microinjection of morphine in the vicinity to the BLC did not alter vocalization thresholds. The present results provide further evidence for the preferential involvement of the amygdala in modulation of the affective component of the pain experience.

Mechanisms of Amygdala Modulation of Hippocampal Plasticity

Basolateral amygdala (BLA) activation by emotional arousal modulates memory-related processes in the hippocampus. We have shown (Akirav and Richter-Levin, 1999b) that activating the BLA before perforant path (PP) tetanization has a biphasic effect on hippocampal plasticity; priming the BLA immediately before PP tetanization results in the enhancement of dentate gyrus (DG) long-term potentiation (LTP) (an "emotional tag"), whereas stimulation in a spaced interval results in the suppression of DG-LTP. Here, we aimed to elucidate the mechanisms underlying BLA modulation of DG-LTP and specifically to examine whether the stress hormones norepinephrine (NE) and corticosterone (CORT) are main mediators of the BLA biphasic effects. We found that the BLA affects hippocampal plasticity in a complex manner; BLA priming enhanced DG-LTP, and both NE and CORT mediated this effect. Furthermore, we found that ipsilateral BLA spaced activation (2 hr before PP tetanization) suppressed DG-LTP and that this suppressive effect was also mediated by NE and CORT. Priming the contralateral BLA enhanced DG-LTP similarly to the ipsilateral enhancement, but neither NE nor CORT mediated this effect. The spaced activation of the contralateral BLA did not suppress DG-LTP. Taken together, these results suggest that differential mechanisms underlie the ipsilateral and contralateral BLA effects on hippocampal plasticity. Hence, the BLA modulates hippocampal memory processes, presumably via the mediation of the stress hormones NE and CORT, to establish a diverse memory of the experience. Possibly, at the onset of an emotional event the stress hormones permissively mediate plasticity. However, their prolonged presence in the system may suppress the cognitive response to stress.

Amygdala Modulation of Memory Consolidation: Interaction with Other Brain Systems

There is a strong consensus that the amygdala is involved in mediating influences of emotional arousal and stress on learning and memory. There is extensive evidence that the basolateral amygdala (BLA) is a critical locus of integration of neuromodulatory influences regulating the consolidation of several forms of memory. Many drug and stress hormone influences converge in activating the release of norepinephrine (NE) within the BLA. Evidence from studies using in vivo microdialysis and high-performance liquid chromatography indicates that increases in amygdala NE levels assessed following inhibitory avoidance training correlate highly with subsequent retention. Other evidence indicates that NE influences on memory consolidation require muscarinic cholinergic activation within the BLA provided by projections from the nucleus basalis magnocellularis (NB). Evidence from several experiments indicates that activation of the BLA plays an essential role in modulating memory consolidation processes involving other brain regions. These findings provide strong support for the hypothesis that the BLA plays a critical role in regulating the consolidation of lasting memories of significant experiences.

Neurobiological mechanisms of emotionally influenced, long-term memory

Publisher Summary Findings from extensive research involving both human and animal subjects converge on the view that modulation of memory storage for emotionally arousing events occurs, at least in part, by an interaction of endogenous stress hormone systems and the amygdala complex. This chapter discusses the key findings supporting this view, including new evidence from human subject studies. While many different stress hormones have been implicated in memory modulation, including adrenocortical hormones, the focus is on the catecholamines, as they have been most consistently implicated in memory. The chapter also addresses another hypothesis of amygdale function in memory— namely, that the amygdala is the place where Pavlovian fear conditioning associations are formed and permanently stored. The findings in this chapter argues strongly against the view that narrative rehearsal is a sufficient explanation of enhanced memory associated with emotional arousal, and provide additional support for amygdala modulation of memory for emotional material.

Involvement of α 1-adrenoceptors in the basolateral amygdala in modulation of memory storage

These experiments examined the involvement of α 1-adrenoceptors in the basolateral amygdala and their interaction with β-adrenoceptors in modulating memory storage. In Experiment 1, male Sprague–Dawley rats, implanted with bilateral cannulae in the basolateral amygdala, were trained in a one-trial inhibitory avoidance task and immediately after training, were given microinfusions (0.2 μl/side) of the selective α 1-adrenoceptor antagonist, prazosin (0.1–1.0 μg). Retention was tested 48 h later. Prazosin induced a dose-dependent impairment in retention performance. In Experiment 2, animals received post-training intra-basolateral amygdala infusions of phenylephrine (a non-selective α-adrenoceptor agonist; 1.0–10.0 μg) alone or in combination with yohimbine (a selective α 2-adrenoceptor antagonist; 0.2 μg) to examine the effects, on memory storage, of selective α 1-adrenoceptor activation. Low doses of phenylephrine alone tended to impair retention performance, whereas the highest dose was non-effective. In contrast, phenylephrine infused together with yohimbine induced a dose-dependent enhancement of retention performance, suggesting that a selective activation of α 1-adrenoceptors enhances memory formation. In Experiment 3, animals received intra-basolateral amygdala infusions of phenylephrine (1.0–10.0 μg) and yohimbine (0.2 μg) in combination with atenolol (a β 1-adrenoceptor antagonist; 1.0 μg). Atenolol blocked the memory-enhancing effects induced by infusions of phenylephrine together with yohimbine. Considered together, these findings suggest that α 1-adrenoceptors in the basolateral amygdala are implicated in mediating the effects of norepinephrine on memory storage and that their action depends on concurrent β-adrenoceptor activation.

Copulatory behavior in male rats with lesions in the bed nucleus of the stria terminalis

Male rats receiving lesions in the bed nucleus of the stria terminalis(BNST) displayed more intromissions preceding each of three ejaculations in a test. BNST-lesion males also tended to be slower in the temporal patterning of copulation. The present data, together with recent reports of corticomedial amygdala modulation of copulation, indicate an involvement of the amygdala-strial system in the achievement of ejaculation and, to a lesser degree, in the temporal aspects of copulation.