Dan Yaniv

Effects of inescapable stress on LTP in the amygdala versus the dentate gyrus of freely behaving rats

Stress impairs hippocampal long‐term potentiation (LTP), a model of synaptic plasticity that is assumed to underlie memory formation. In the amygdala, little is known about the effects of stress on LTP, or about its longevity. Here we assessed the ability of entorhinal cortex (EC) stimulation to induce LTP simultaneously in the basal amygdaloid nucleus (B) and in the dentate gyrus (DG) of freely behaving Wistar rats. We also tested whether LTP persists over days. Once established, we investigated the effects of acute vs. repeated inescapable stressful experiences on LTP in both structures. Results show that B, like DG, sustained LTP for 7 days. Furthermore, a single exposure to moderate stress facilitated LTP in B but did not affect DG LTP. Stress re‐exposure inhibited LTP in DG but only long‐lasting LTP (>3 days) in B. Behaviourally, animals exhibited a higher immobility when re‐exposed to the stressor than with a single/first exposure. These data support a role for B in memory storage. Furthermore, they support a differential involvement of the amygdala and hippocampus in memory formation and storage depending on the emotional characteristics of the experience.

Glucocorticoid receptors and β-adrenoceptors in basolateral amygdala modulate synaptic plasticity in hippocampal dentate gyrus, but not in area CA1

The basolateral amygdala (BLA) is a key structure in a memory-modulatory system that regulates stress and stress hormones (glucocorticoid and noradrenaline) effects on hippocampal functioning. We have shown previously that priming the amygdala differentially affects plasticity in the hippocampal dentate gyrus (DG) and CA1, and mimicked acute stress effect on plasticity in these two subregions. In the present study, we investigated the mechanisms that mobilize the BLA to differentially alter plasticity in DG and CA1. Glucocorticoid receptors antagonist RU 38486 or beta-adrenoceptor antagonist propranolol were microinfused in the BLA, 10 min prior to BLA activation-induced modulation of long-term potentiation (LTP) in DG and CA1. The results showed that neither glucocorticoid nor noradrenergic transmissions in the BLA are necessary for LTP induction and for the impairing effect of amygdala activation on CA1 LTP. In contrast, blockade of glucocorticoid or noradrenergic transmission in BLA, increased baseline synaptic transmission in the DG, but suppressed the enhancing effect of BLA activation on DG LTP. These findings provide further evidence for a differential amygdala control of hippocampal subregions as well as for differential memory processes involving CA1 and DG. They also provide insight into how stress hormones exert their actions on the circuits involved in these processes.

Simultaneous induction of long-term potentiation in the hippocampus and the amygdala by entorhinal cortex activation: mechanistic and temporal profiles.

The medial temporal lobe, including the entorhinal cortex, the amygdala and the hippocampus, has an important role in learning and memory, and its circuits exhibit synaptic plasticity (long-term potentiation [LTP]). The entorhinal cortex is positioned to exert a potent influence on the amygdala and the hippocampus given its extensive monosynaptic projections to both areas. We therefore studied the effects of activation of the entorhinal cortex with simultaneous recording of LTP in the hippocampus and amygdala in the anesthetized rat. theta Burst stimulation of the lateral entorhinal cortex induced LTP simultaneously in the basal amygdaloid nucleus and in the dentate gyrus. However, the mechanisms involved in the induction of LTP in the two areas differed. The N-methyl-D-aspartate receptor antagonist 3-[(+/-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid delivered 1 h before LTP induction (10 mg/kg, i.p.), blocked LTP in the dentate gyrus but not in the amygdala. In addition we found that the basal amygdala as well as the dentate gyrus sustained late-phase LTP (10 h) which may participate in memory encoding and/or modulation processes. Overall, the results suggest a coordinating role for the entorhinal cortex by simultaneously modulating activity and plasticity in these structures, albeit through different mechanisms. Interactive encoding of this sort is believed to endow memories with a different, more integrative, quality than when either pathway is activated alone.

A gradient of plasticity in the amygdala revealed by cortical and subcortical stimulation, in vivo

Projections to the amygdala from various cortical and subcortical areas terminate in different nuclei. In the present study we examined long-term potentiation of synaptic transmission in the lateral or the basal amygdaloid nuclei by theta burst stimulation of thalamic vs. cortical sensory projections in the anesthetized rat. Although both the medial geniculate nucleus and the dorsal perirhinal cortex have direct projections to lateral nucleus, only the thalamic stimulation induced long-term potentiation of field potentials recorded in the lateral nucleus. In contrast, cortical (ventral perirhinal cortex) but not thalamic stimulation induced long-term potentiation in the basal nucleus. Since the thalamic pathway is believed to process simple/unimodal stimulus features, and the perirhinal cortex complex/polymodal sensory representations, the dissociation of long-term potentiation in lateral and basal nuclei suggests that the basal nucleus may serve as an amygdaloid sensory interface for complex stimulus information similar to the role of the lateral nucleus in relation to relatively simple representations. Thus plasticity of simple and complex representations may involve different amygdala inputs and circuits.

LTP in the rat basal amygdala induced by perirhinal cortex stimulation in vivo.

The present study examined the effects of ventral perirhinal cortex (vPRC) stimulation on evoked field potentials (EPs) in the basal amygdala (BN), using extracellular recording techniques. Single pulse stimulation of the vPRC reliably evoked a negative field potential in the BN that was missing in the lateral nucleus. Paired-pulses delivered to the vPRC induced a short-lasting facilitation at intervals between 15 and 120 ms. Application of brief theta burst stimulation to the vPRC produced an enduring long-term potentiation (LTP) that reached 150% of control values. The induction of LTP was not accompanied by a decrease in paired-pulse facilitation. These results suggest that emotional learning involving complex stimulus representations may be mediated by cortico-amygdalar projections amenable to LTP.

Perirhinal cortex and thalamic stimulation induces LTP in different areas of the amygdala

The parahippocampal region consists of the cortical areas that surround the hippocampus, including the perirhinal, the postrhinal, and entorhinal cortices. To a large degree, research into parahippocampal function is guided by the view that this area mediates interactions between cerebral cortex and hippocampus and thus contributes to object memory (association of objects with events) (see, for example, Suzuki et al.1 and Murray2). Yet in recent years the amygdala and the perirhinal cortex (PRC) have been increasingly implicated in several aspects of cognitive and emotional learning, that is, associating objects/contexts with affective valences (for reviews, see Refs. 3–5). In fact, the rat PRC is regarded as a “gateway” for cortical sensory input to the amygdala,6 before the input is further transferred to diencephalic motivational systems that regulate behavior. A recent anatomical account of the PRC–amygdala system has distinguished between efferents arising from dorsal and ventral PRC.7 The evidence indicated that the lateral nucleus of the amygdala (LA) receives input from the dorsal bank of the PRC (Brodmann’s area 36), whereas both the fundus and ventral bank of the rhinal sulcus (Brodmann’s area 35; vPRC) project heavily to the amygdaloid basal nucleus (B). In line with these data, we have recently characterized evoked-field potentials (EPs) in the vPRC-B pathway, and showed that these EPs are amenable to long-term potentiation (LTP) in vivo.8 Given the essential role of the amygdala in the formation of emotional memories and that the PRC is involved in processing of complex, polymodal stimuli in both humans (e.g., Bohbot et al.9) and laboratory animals (reviewed by Suzuki,4 but see Bussey et al.10), we suggested that higher order stimulus representations may gain their affective associations via cortical pathways to B which, presumably, functions as a highly integrative site within the amygdaloid processing circuitry.8,11 This suggestion is consistent with a previous study showing that LTP can be induced in vivo by stimulation of hippocampal inputs to B12 and seems complementary to an extensive body of research implicating the LA as an essential component of the circuitry through which (unimodal) auditory stimuli are endowed with