Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

Abstract

Quantitative in situ hybridization revealed that following the induction of hippocampal long-term potentiation (LTP) in the dentate gyms of freely moving rats, specific increases in the expression of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor and mGluRlc, a short splice variant of the metabotropic glutamate receptors that are linked intracellularly to phospholipase C (PLC) and protein kinase C (PKC), were seen in the postsynaptic dentate granule cells. There were no changes in the expression of NR2A; NR2C and NR2D NMDA receptor subunits; or mGluRla, mGluRlb, mGluR5a, and mGluR5b PLC-associated metabotropic receptors. The elevations in NR2B and mGluRlc mRNA were delayed, occurring days after LTP induction. NR2B expression was enhanced significantly by 48 hr after LTP but was starting to decrease toward basal levels by 96 hr. The transient increase in the expression of NR2B mirrored the increase in the expression of PKC-sensitive isoforms of the NR1 subunits of the NMDA 4Corresponding author. receptor we observed previously (Thomas et al. 1994a). The increase in mGluRlc expression was more persistent, showing a significant increase 96 hr after LTP. This study demonstrates that not only are there changes in the expression of individual glutamate receptor subunits but the increases in their expression occur days after the induction of LTP and may reflect so-called late-onset genes that may be important for the maintenance of LTP.

Amygdala infusions of an NR2B-selective or an NR2A-preferring NMDA receptor antagonist differentially influence fear conditioning and expression in the fear-potentiated startle test

“…Many studies have now shown that the ratio of NR2A to NR2B protein or message is dynamic-changing in response to LTP induction (Thomas et al 1996;Williams et al 1998), stress (Bartanusz et al 1995), synaptic activity (Ehlers 2003), NMDA receptor blockade (Bartanusz et al 1995;Fujisawa and Aoki 2003), development (Laurie et al 1997;Lopez de Armentia and Sah 2003), and several other manipulations (Lu et al 2005;Wu et al 2005). Thus, differences in the relative proportions of NR2A to NR2B subunits in rats from different laboratories or suppliers or both may contribute to the variable effects on fear expression of nonselective NMDA receptor antagonists, and perhaps also to variable assessments of the contribution of NMDA receptors to synaptic transmission in amygdala pathways (Li et al 1996;Mahanty and Sah 1999;Weisskopf and LeDoux 1999;Szinyei et al 2003).…”

Long-Term Potentiation and Memory

“…This role for mGluR5 in fear conditioning is consistent with the earlier finding that 1-aminoindan-1,5-dicarboxylic acid (AIDA) resulted in a retention deficit in conditioning to the context but not the cue (103). In contrast to the change in mGluR5 expression, Reidel et al (511) reported that there was no change in mGluR1 expression after fear conditioning, although an increase in mGluR1 mRNA has been observed after induction of LTP in dentate gyrus (611).…”

MAPK, CREB andzif268are all required for the consolidation of recognition memory

“…The evidence came from two main sources: the fact that inhibitors of either protein synthesis (Krug et al 1984;Otani & Abraham 1989;Frey & Morris 1997) or transcription (Nguyen et al 1994) affect the duration of LTP; and the finding that LTP itself induces transcriptional regulation of a variety of genes, including inducible transcription factors (Cole et al 1989;Wisden et al 1990;Abraham et al 1993;Worley et al 1993;French et al 2001) and genes encoding synaptic proteins (e.g. Smirnova et al 1993;Thomas et al 1994Thomas et al , 1996Link et al 1995;Lyford et al 1995;Bramham et al 1996;Hicks et al 1997;Génin et al 2001). Remarkably, experimental evidence also indicates that the expression of long-term memories shares many characteristics with LTP, including similar molecular mechanisms, a requirement for protein synthesis (Davis & Squire 1984;Meiri & Rosenblum 1998) and, in specific areas of the brain, the regulated transcription of a variety of genes (Nikolaev et al 1992;Davis et al 1996Davis et al , 1998Okuno & Miyashita 1996;Guzowski et al 1999Guzowski et al , 2001Tischmeyer & Grimm 1999;Hall et al 2000;Zhao et al 2000;Cavallaro et al 2001).…”