Synaptic NMDA receptors in developing mouse hippocampal neurones: functional properties and sensitivity to ifenprodil.

Abstract

1. Whole-cell patch-clamp techniques were used to record pharmacologically isolated NMDA receptor-mediated EPSCs (NMDA EPSCs) from CAl pyramidal cells (PCs) receptor channels) and its further prolongation by depolarization in young PCs are consistent with heightened NMDA-dependent neuronal plasticity early in development. The agerelated changes in these properties may result from a developmental change in NMDA receptor subunit composition.The N-methyl-D-aspartate (NMDA) subtype of glutamate ment. Thus, the decay kinetics of NMDA receptor-mediated receptors plays a major role in central synaptic transmission excitatory postsynaptic currents (NMDA EPSCs) become (e.g.

Functional Maturation of the First Synapse in Olfaction: Development and Adult Neurogenesis

“…3). The presence of NR2B subunits that do not determine NMDA receptor decay kinetics has previously been observed in hippocampal neurons (Kirson and Yaari, 1996;Ye et al, 2005), where decay kinetics are presumed to be set by other NR2 subunits. Indeed, NR2C-or NR2D-containing NMDA receptors are associated with slow decay constants (Monyer et al, 1992), and both subunits are known to be expressed in the OB (Wenzel et al, 1995), suggesting that NR1-NR2C/D heteromeric channels may be responsible for setting the lower limit on (nonmaturing) NMDA response kinetics at the ON-to-OB synapse.…”

Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons

“…We should also consider, however, that the lack of correlation between deactivation kinetics and pharmacological sensitivity in distinct age groups might not be related only to distinct deactivation properties of NMDA receptors with different subunit compositions; rather it may reflect possible post-translational modifications that can produce longer series of channel openings (Lieberman & Mody, 1994;Yu, Askalan, Keil & Salter, 1997). Recently, antagonism of hippocampal NMDA-mediated synaptic currents by ifenprodil has been shown to be dependent on development (Kirson & Yaari, 1996), implying a developmental decrease in synaptic receptors comprising the NR2B subunit. At the same time, two reports have attempted to correlate the presence of mRNA for NMDA receptor subunits with the decay kinetics of eN_EPSCs in neurons in brain slices (Flint et al 1997;Plant et al 1997).…”

“…At the same time, recent studies have identified pharmacological agents which are able to antagonize in a selective manner NMDARs containing the NR1ÏNR2B subunits; these include ifenprodil (Williams, 1993), haloperidol (Ilyin, Wittermore, Guastella, Weber & Woodward, 1996) and the novel ifenprodil derivative, CP101,606 (Chenard et al 1995;Boeckman & Aizenman, 1996). Recently, antagonism of hippocampal NMDA-mediated synaptic currents by ifenprodil has been shown to be dependent on development (Kirson & Yaari, 1996), implying a developmental decrease in synaptic receptors comprising the NR2B subunit. At the same time, two reports have attempted to correlate the presence of mRNA for NMDA receptor subunits with the decay kinetics of N_EPSCs in neurons in brain slices (Flint et al 1997;Plant, Schirra, Garashuck, Rossier & Konnerth, 1997).…”

Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development

“…NMDARs are composed of two obligatory NR1 subunits and two NR2 subunits, of which there are four members (NR2A-D) (8). NR2B-NMDARs are expressed during synaptogenesis and are replaced by NR2A-NMDARs during synapse maturation (9-11), a replacement that accounts for the developmental decrease in the NMDAR excitatory postsynaptic current (EPSC) decay time (12,13) and the loss of sensitivity to the NR2B antagonist ifenprodil (14). The precise molecular mechanisms underlying the differential synaptic trafficking of AMPAR and NMDAR during developmental synaptogenesis and maturation remain largely unknown.…”