Induction of long‐term potentiation in the basolateral amygdala does not depend on NMDA receptor activation

Abstract

Long-term potentiation (LTP) can be induced in the lateral and basolateral amygdala by stimulating synaptic afferents in the external capsule (EC). We examined the sensitivity of amygdaloid LTP to the NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5), which is known to block LTP induction in the Schaffer collateral/CA1 synapses in the hippocampus. While relatively high concentrations (100 microM) of DL-AP5 were effective in preventing LTP induction in the lateral and basolateral amygdala in vitro, the same concentrations also significantly depressed synaptic responses to low-frequency stimulation. Furthermore, at 50 microM, a concentration sufficient to block both synaptic responses mediated by NMDA receptors and LTP induction in the hippocampus and neocortex, AP5 did not affect the probability of inducing LTP in the amygdala. Application of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which blocks non-NMDA excitatory amino acid receptors, reduced the monosynaptic response to EC stimulation by 85%. The remaining CNQX-insensitive response did not appear to be mediated by NMDA-type receptors, since it was not reduced by 50 or 100 microM AP5, and showed none of the voltage sensitivity characteristic of NMDA responses. These data suggest that while the induction of LTP in the amygdala produced by EC stimulation is blocked by high doses of AP5, plasticity at these synapses probably does not require activation of NMDA receptors.

Increased Fear Learning Coincides with Neuronal Dysinhibition and Facilitated LTP in the Basolateral Amygdala following Benzodiazepine Withdrawal in Rats

“…In support of this possibility concurs the fact that the great majority (93%) of prefrontal-amygdala synapses identified in the BLA are located on dendritic spines of pyramidal projection cells and belong to the asymmetric (excitatory) type (Brinley-Reed et al, 1995). Moreover, EC stimulation has been shown to evoke monosynaptic excitatory postsynaptic potentials (EPSP) in BLA neurons (Chapman and Bellavance, 1992;Li et al, 1998;Mahanty and Sah, 1998;Chapman et al, 1990). Since interneurons represent a minority (o15%) of BLA neurons (McDonald, 1982;Millhouse and De Olmos, 1983), it is unlikely that their firing would have contributed significantly to the generation of the PS.…”

“…It has been demonstrated that activation of amygdala afferents in the EC (Chapman et al, 1990;Chapman and Bellavance, 1992) or in the LA (Rainnie et al, 1991b) elicit IPSPs that are superimposed or follow the EPSP of BLA neurons referred to above. These IPSPs are GABAergic and are elicited by direct or recurrent activation of local interneurons (Preleviç et al, 1976;Rainnie et al, 1991b); suppressing GABAergic transmission has been shown to result in increased excitability (Wang et al, 2002(Wang et al, , 2001) and epileptiform activity (Chapman et al, 1990; Gean and Shinnick-Gallagher, 1987; Gean et al, 1989).…”

“…Post hoc analysis indicated significant differences (po0.05) with 20 and 40 ms of interstimulus interval. This lack of PPI in withdrawn animals may be attributed to a decrease of the GABA-dependent IPSP that occurs simultaneously or following the EPSP evoked by EC stimulation (Wang et al, 2001;Rainnie et al, 1991b, a;Chapman and Bellavance, 1992). Interestingly, although the PS was not smaller in the response to the second stimulus, the secondary repetitive spikes were suppressed (Figure 5a).…”

“…Paired pulse stimulation represents a tool for analysis of the excitation-inhibition cycle in neuronal networks (Marder and Buonomano, 2003), including the amygdala (Roberto et al, 2003;Wang et al, 2002;Rammes et al, 2000); short interstimulus interval-dependent paired pulse inhibition (PPI) is considered to depend on an IPSP that is GABA A mediated (Roberto et al, 2003;Marder and Buonomano, 2003;Delaney and Sah, 2001;Chapman and Bellavance, 1992;Braga et al, 2002;Adamec et al, 1981). Taking into account the results just described, we used PPI to evaluate the GABAergic inhibitory activity in BLA neurons, with the prospect of defining differences between control and withdrawn animals.…”

Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP

“…Although the evidence for the importance of LTP in hippocampal function is clearly substantial, LTP is not an exclusive property of the hippocampus. It can be observed in other brain regions including the somatosensory [8,9], visual [35,36], auditory [37], olfactory [11,52], motor [2], piriform [33], entorhinal [17], cingulate [27] cortices, the amygdala [42,10] and thalamo-cortical synapses [13]. Furthermore, a higher elevation of intracellular Ca 2 + levels is associated with LTP and a smaller increase of Ca 2 + is seen when long-term depression (LTD) is induced [3,41].…”