Kainate receptors are involved in synaptic plasticity

Abstract

The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are three classes of ionotropic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate receptors; critical roles in synaptic plasticity have been identified for two of these. Thus, at many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors. Here, to determine whether kainate receptors are involved in synaptic plasticity, we have used a new antagonist, LY382884 ((3S, 4aR, 6S, 8aR)-6-((4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydro isoquinoline-3-carboxylic acid), which antagonizes kainate receptors at concentrations that do not affect AMPA or NMDA receptors. We find that LY382884 is a selective antagonist at neuronal kainate receptors containing the GluR5 subunit. It has no effect on long-term potentiation (LTP) that is dependent on NMDA receptors but prevents the induction of mossy fibre LTP, which is independent of NMDA receptors. Thus, kainate receptors can act as the induction trigger for long-term changes in synaptic transmission.

Generalist genes analysis of DNA markers associated with mathematical ability and disability reveals shared influence across ages and abilities

“…Although MMP7 is involved in the breakdown of extracellular matrix during normal physiological processes such as embryonic development, growth and tissue repair [24], GRIK1 and DNAH5 have more direct links to the brain. GRIK1 encodes a glutamate receptor which mediates neurotransmission and synaptic plasticity [25,26], and dysfunction of this gene is implicated in a number of psychiatric phenotypes [27,28]. DNAH5 encodes the dynein axonemal heavy chain 5 protein, which is the force-generating component of cilia, the correct functioning of which is essential in all areas of embryonic growth [29]; DNAH5 in particular has been demonstrated as vital for normal brain development [30].…”

Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid

“…Analytical thin-layer chromatography (TLC) was carried out using Merck Silica gel 60 F254 aluminum sheets. Compounds were detected as single spots on TLC plates and visualized using UV light (254 or 366 nm) and KMnO 4 or ninhydrin. Merck silica gel (35-70 mesh) was used for flash chromatography.…”

“…The reaction mixture was allowed to warm up to -50°C and stirred at this temperature for 1 h. The reaction was quenched with sat. NH 4 (…”

Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex

“…The role of GluR5-containing KARs was determined using selective agonists and antagonists. ATPA is a selective GluR5 agonist (Clarke et al, 1997) and the GluR5 subunit is selectively blocked by LY382884 (Bleakman et al, 1996;Bortolotto et al, 1999). Fig.…”