Comparison of paired‐pulse facilitation of AMPA and NMDA synaptic currents in the lateral amygdala

Abstract

Stimulating thalamic fibers exiting from the internal capsule evokes a glutamatergic excitatory postsynaptic current (EPSC) recorded in vitro with patch electrodes in neurons of the rat lateral amygdala (LA). The purpose of this study is to compare paired-pulse facilitation (PPF), a form of short-term synaptic plasticity, of AMPA and NMDA receptor-mediated EPSCs. Analysis of PPF at this synapse is important since, in fear-conditioned animals, PPF reflects an enhanced transmitter release but the amplitude of only AMPA EPSCs is facilitated. PPF magnitude of the composite EPSC is a result of both AMPA and NMDA receptor activation; however, the characteristics of AMPA and NMDA PPF are dissimilar. Specifically, the NMDA EPSC shows greater PPF (NMDA PPF) than does the AMPA EPSC whether measuring the NMDA PPF magnitude in an AMPA antagonist/Mg(2+)-free solution or by subtracting the AMPA EPSC from the composite EPSC in normal Mg(2+). Presynaptic NMDA receptors neither influence AMPA PPF nor account for the difference between the NMDA and AMPA PPF. Another difference was that removal of inhibitory tone enhanced AMPA PPF, while it had mixed effects on NMDA PPF. Furthermore, AMPA PPF was independent of stimulus intensity and postsynaptic voltage, unlike the NMDA PPF. Another dissimilarity was that the amplitudes of pairs of AMPA EPSCs were not correlated, suggesting presynaptic mechanisms. In contrast, NMDA PPF was dependent on stimulus intensity and postsynaptic voltage and the amplitudes of paired NMDA EPSCs had a positive correlation, suggesting a postsynaptic influence. Both AMPA and NMDA PPF were influenced by GABA inhibition and this could be a factor in the magnitude disparity. These data show that AMPA and NMDA PPF have different characteristics and contribute to the composite PPF in the thalamic to lateral amygdala pathway.

Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning

“…1E). This finding suggests a presynaptic modification leading to an increase in neurotransmitter release probability (32), a process that might account for the observed potentiation of postsynaptic NMDA currents. Consistent with this hypothesis, bath application of DOI increased the frequency of AMPA-mediated miniature EPSCs (mEPSCs) in lowmagnesium ACSF (baseline: 7.94 ± 0.86 Hz, DOI: 11.65 ± 0.95 Hz; P < 0.001) (Fig.…”

“…NMDA paired-pulse facilitation was performed in the same conditions as for NMDA EPSC recording, as previously described (32). Briefly, two NMDA EPSCs (EPSC1 and EPSC2) were evoked at 20 Hz, 10 times at 10-s intervals before and after 10 min of DOI perfusion.…”

Differential Roles of mGluR1 and mGluR5 in Brief and Prolonged Nociceptive Processing in Central Amygdala Neurons

“…The amygdala is composed of several anatomically and functionally distinct nuclei. Particularly the lateral and basolateral amygdaloid nuclei (LA and BLA) have been shown to exhibit a high degree of plasticity in various models of long-term synaptic and behavioral modification (Blair et al 2001;Keele et al 2000;LeDoux 2000;Lin et al 2000;Neugebauer et al 1997;Zinebi et al 2001). …”

Down-Regulation of Synaptic GluN2B Subunit-Containing N-methyl-d-aspartate Receptors: A Physiological Brake on CA1 Neuron α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Hyperexcitability during Benzodiazepine Withdrawal

“…Potentiation of AMPAR function in hippocampus was associated with GluA1 homomer incorporation into CA1 pyramidal synapses (Song et al, 2007;Shen et al, 2010) and positively correlated with benzodiazepine withdrawal anxiety (Izzo et al, 2001;Xiang and Tietz, 2007), as well as other animal models of anxiety ). An LTP-like modulation of excitatory responses and AMPAR responses was also found in amygdala neurons of fear-conditioned rats (Zinebi et al, 2001;Iosoardi et al, 2004), another key locus within the neural circuit mediating anxiety (McNaughton and Gray, 2000). On the contrary, maintenance of fear conditioning, in which Pavlovian contingencies induced fear and anxiety, was associated with decreased expression of both GluN2A and GluN2B subunits and proposed to guard against enhanced glutamatergic strength or serve as a mechanism to rapidly reactivate emotional memories through rapid NMDAR recycling (Zinebi et al, 2003).…”

“…5), previously shown to lead to the disappearance of withdrawal anxiety (Van Sickle et al, 2004). Thus the depression of NMDAR function during FZP withdrawal may act as a compensatory negative feedback mechanism to protect the neuron from AMPAR-mediated overactivation as in amygdala neurons during fear conditioning (Zinebi et al, 2001(Zinebi et al, , 2003, striatal neurons after chronic amphetamine exposure (Mao et al, 2009), or spinal cord nociceptive synapses during chronic peripheral inflammation (Vikman et al, 2008). The reduction of GluN2B subunit-mediated NMDAR currents would serve as a homeostatic mechanism to offset neuronal hyperactivity generated by the progressive enhancement of AMPAR current and thus may serve as a physiological brake to down-regulate neuronal output, limiting withdrawal symptoms such as anxiety.…”