Isolated NMDA receptor-mediated synaptic responses express both LTP and LTD

Abstract

1. The possibility of use-dependent, long-lasting modifications of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission was examined by intracellular recordings from granule cells of the hippocampal dentate gyrus in vitro. In the presence of the non-NMDA receptor antagonist 6-cyano-7-nitroquinaxaline-2,3-dione (CNQX, 10 microM) robust, long-term potentiation (LTP) of NMDA receptor-mediated synaptic potentials was induced by brief, high (50 Hz) and lower (10 Hz) frequency tetanic stimuli of glutamatergic afferents (60 +/- 6%, n = 8, P less than 0.001 and 43 +/- 12%, n = 3, P less than 0.05, respectively). 2. Hyperpolarization of granule cell membrane potential to -100 mV during 50-Hz tetanic stimuli reversibly blocked the induction of LTP (-6 +/- 2%, n = 6, P greater than 0.05) indicating that simultaneous activation of pre- and postsynaptic elements is a prerequisite for potentiation of NMDA receptor-mediated synaptic transmission. In contrast, hyperpolarization of the granule cell membrane potential to -100 mV during 10-Hz tetanic stimuli resulted in long-term depression (LTD) of NMDA receptor-mediated synaptic potentials (-34 +/- 8%, n = 8, P less than 0.01). 3. We also studied the role of [Ca2+]i in the induction of LTP and LTD of NMDA receptor-mediated synaptic responses. Before tetanization, [Ca2+]i was buffered by iontophoretic injections of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). BAPTA completely blocked the induction of LTP (3 +/- 5%, n = 13) and partially blocked LTD (-14.8 +/- 6%, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of NMDA receptor channels to the expression of LTP in the hippocampal dentate gyrus

“…Our laboratory has previously shown that pharmacologically isolated NMDARs can express LTP in the presence of reduced concentrations of Mg 2ϩ , or at depolarizing potentials in the presence of normal Mg 2ϩ (Xie et al, 1992). In the present study, we further test the possibility that NMDARs express LTP in the presence of normal Mg 2ϩ and in response to physiological patterns of afferent stimulation.…”

“…Hippocampal slices were prepared from New Zealand white rabbits as by Xie et al (1992). Briefly, transverse hippocampal slices (500-m thick) were cut with a vibratome and were incubated in medium consisting of (in mM): NaCl, 126; KCl, 3; NaH 2 PO 4 , 1.25; NaHCO 3 , 26; glucose, 10; CaCl 2 , 2; MgSO 4 , 2, aerated with 95% O 2 /5% CO 2 .…”

“…Whether or not potentiation of NMDARs themselves can be induced by HFS has been an issue of debate. LTP can be induced by HFS in pharmacologically isolated NMDARs (Bashir et al, 1991;Xie et al, 1992; but see Kauer et al, 1988;. Potentiation of NMDA component also has been re-ported in studies in which the NMDA component was isolated only for measurement before and after LTP induction, but not during the LTP induction phase Clark and Collingridge, 1995;O'Connor et al, 1995;Xiao et al, 1996;Bayazitov and Kleschevnikov, 2000; but see Muller et al, 1989;Perkel and Nicoll, 1993).…”

Extrasynaptic NR2D-Containing NMDARs Are Recruited to the Synapse during LTP of NMDAR-EPSCs

“…Numerous studies have shown that long-term potentiation (LTP) and long-term depression (LTD) of NMDAR transmission can be induced by increased presynaptic activity. In particular, high-frequency stimulation (HFS) rapidly induces LTP of NMDAR-EPSPs/EPSCs in the hippocampal dentate gyrus (O'Connor et al, 1994(O'Connor et al, , 1995Harney et al, 2006), CA1 (Bashir et al, 1991;Berretta et al, 1991;Asztely et al, 1992;Xie et al, 1992;Clark and Collingridge, 1995;Kullmann et al, 1996;Jia et al, 1998;Grosshans et al, 2002;Kotecha et al, 2003;Lozovaya et al, 2004), and CA3 (Kwon and Castillo, 2008;Rebola et al, 2008) (for review, see Lau and Zukin, 2007). LTD of NMDAR-EPSCs can also be induced by low-frequency stimulation (Morishita et al, 2005) or by HFS under conditions of relatively high intracellular Ca 2ϩ buffering (Harney et al, 2006).…”

Contribution of T‐type VDCC to TEA‐induced long‐term synaptic modification in hippocampal CA1 and dentate gyrus

“…In DG granule cells, the enhancement of depolarization by TEA was much weaker compared with that in CA1 and, as a consequence, the Ca 2ϩ influx was much reduced. It has been established that low levels of Ca 2ϩ influx are associated with LTD, as we observed for the DG (Xie et al, 1992). Our experiments and simulations were carried out on CA1 pyramidal cells and DG granule cells; studies of CA3 pyramidal cell were not included in our analyses.…”