Amygdala stimulation modulates hippocampal synaptic plasticity

Abstract

Experience-dependent synaptic plasticity is a fundamental feature of neural networks involved in the encoding of information, and the capability of synapses to express plasticity is itself activitydependent. Here, we introduce a ''low-frequency burst stimulation'' protocol, which can readily induce both long-term potentiation (LTP) and long-term depression (LTD) at in vivo medial perforant path-dentate gyrus synapses. By varying stimulation parameters, we were able to build a stimulus-response map of synaptic plasticity as a LTP-LTD continuum. The response curve displayed a bidirectional shift toward LTP and LTD, depending on the degree and timing of neural activity of the basolateral amygdala. The range of this plastic modulation was also modified by past activity of the basolateral amygdala, suggesting that the amygdala can arrange its ability to regulate the dentate plastic responses. The effects of the BLA activation were replicated by stimulation of the lateral perforant path and, hence, BLA stimulation may recruit the lateral entorhinal cortex. These results represent a high-order dimension of heterosynaptic modulations of hippocampal synaptic plasticity.BCM theory ͉ metaplasticity ͉ long-term potentiation ͉ long-term depression ͉ dentate gyrus T he amygdala plays an important role in emotional arousal and has emerged as a key modulator of memory storage in other brain regions (1, 2). Behavioral studies have indicated that microinjections of diverse pharmacological agents such as glucocorticoid-receptor agonists, ␤-adrenergic agents, amphetamine, and local anesthetics into the basolateral amygdala (BLA) enhance or impair hippocampus-dependent memory (3-7).In support of these studies, we and other groups have reported that BLA activation͞inactivation or delivery of glutamatergic and ␤-adrenergic agents into the BLA can modulate long-term potentiation (LTP) at the medial perforant path (MPP)-dentate gyrus (DG) synapses in the hippocampal formation (8-13). Prior stimulation of the BLA is also capable of gating subsequent induction of LTP in the DG (14, 15). The BLA modulation of hippocampal LTP is, therefore, a compelling candidate mechanism underlying the amygdalar control of the hippocampal memory system.In this respect, however, several issues remain to be resolved. For example, it is uncertain which brain region relays BLA inputs to the DG, which dentate substratum ultimately receives the BLA input, whether the BLA also modulates hippocampal long-term depression (LTD), or how various patterns of BLA activity alter its ability to modulate DG plasticity. In particular, the last two questions have been difficult to address because there is no simple experimental system that can reliably induce homosynaptic LTD in vivo; note that, unlike the case of slice preparations, in vivo LTD is usually inducible only when the synapses are electrically or pharmacologically primed before a LTD-inducing stimulus (16)(17)(18)(19).In the present work, we describe an in vivo protocol of low-frequency burst stimulation (LFBS),...

Bidirectional Modulation of Hippocampal Long-Term Potentiation under Stress and No-Stress Conditions in Basolateral Amygdala-Lesioned and Intact Rats

“…Under low or moderate stress conditions, both types of reinforcement of DG-LTP have been shown to depend on noradrenergic and cholinergic activation (Ikegaya et al, 1997;Jas et al, 2000;Frey et al, 2001;Straube et al, 2003) and can be modulated by the basolateral amygdala Izquierdo, 1994;Ikegaya et al, 1996Ikegaya et al, , 1997Almaguer-Melian et al, 2003, Nakao et al, 2004. After acute swim stress, we found that DG-LTP reinforcement was dependent on the activation of mineralocorticoid receptors (MRs) by binding of corticosterone .…”

“…Additional work is required to characterize specific properties of LTP modulation induced by different tetanization protocols. Nakao et al (2004) found that modulation of DG synaptic plasticity critically depends on the interplay of the stimulation strengths of the BLA and the perforant path. They propose a direct synaptic input from the BLA to the dentate gyrus via the lateral entorhinal cortex and lateral perforant path.…”

Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection

“…52,53 Therefore, as proposed by Benes,58 and based on the data reported in this study, one can hypothesize that the selective decrease in GABAergic inhibitory function observed in layer I of SZP PFC may be the consequence of a specific disorganization of the complex neuronal afferent network reaching GABAergic interneurons of layers I and II from the amygdala or other cortico-limbic regions. [58][59][60][61] In schizophrenia, the disorganization of the MD afferent network reaching the GABAergic interneurons of the deeper cortical layers may be less pronounced or localized to only a small subset of neurons such as the chandelier neurons, which have been shown to be dysfunctional in SZP. 23 Is DNMT1 overexpression in layer I cortical GABAergic neurons causally related to the decrease of GAD 67 and reelin?…”

“…In contrast, the burst-spiking horizontal and bitufted cells of layers I and II receive on their dendrites both excitatory axon terminal projections from thalamus and cortico-cortical pyramidal neurons 53 and massive excitatory axon terminal projections from the basolateral nucleus of the amygdala. [58][59][60][61] It has been suggested that amygdalo-cortical or cortico-cortical excitatory inputs to layer I and II cortical GABAergic interneurons may help to suppress information arriving at distal pyramidal neuron dendrites and den-dritic spines directly from MD afferent synapses. 52,53 Therefore, as proposed by Benes,58 and based on the data reported in this study, one can hypothesize that the selective decrease in GABAergic inhibitory function observed in layer I of SZP PFC may be the consequence of a specific disorganization of the complex neuronal afferent network reaching GABAergic interneurons of layers I and II from the amygdala or other cortico-limbic regions.…”

Mechanisms of heterosynaptic metaplasticity

“…R. Soc. B 369: 20130148 the induction of such effects in both the hippocampus [43] and prefrontal cortex [44], albeit thus far only when the timing between amygdala stimulation and plasticity induction is short.…”