Kainate receptors hippocampus

The role of the kainate receptor system in the brain is at an early stage since there are as yet few pharmacological tools to study its function. However, mutations in the kainate receptor genes have been made in mice and there is a GluR6 kainate receptor knock-out mouse. Kainate binding is absent in areas of the brain which normally have high levels such as the hippocampus. Here, in normal animals kainate receptors mediate a postsynaptic current which is absent in the GluR6 knock-out mouse. The mice have... 

Kainate receptors mediate a depression of evoked excitatory synaptic transmission in areas CA1 (40,88-90) and CA3 (35,37,91,92) of the hippocampus. There is strong evidence that in area CA1 the locus of this effect is presynaptic. Thus, activation of kainate receptors depresses release of L-glutamate from synaptosomes (88) and depresses both NMDA and AMPA receptor-mediated components of the evoked EPSC in parallel (88,90). Furthermore, the effects of kainate receptor activation on excitatory synaptic transmission in CA1 are associated with changes in presynaptic Ca2+ (89), an increase in paired-pulse facilitation (35,88,89), and a reduction in quantal content, as assessed using 1/CV2, but no change in mEPSC amplitude (90). 

Kullmann, D. M. (2001) Presynaptic kainate receptors in the hippocampus slowly emerging from obscurity. Neuron 32, 561-564. 

Contractor, A., Swanson, G., and Heinemann, S. F. (2001) Kainate receptors are involved in short- and long-term plasticity at mossy fiber synapses in the hippocampus. Neuron 29, 209-216. 

Frerking, M., Schmitz, D., Zhou, Q., Johansen, J., and Nicoll, R. A. (2001) Kainate receptors depress excitatory synaptic transmission at CA3-CA1 synapses in the hippocampus via a direct presynaptic action. J. Neurosci. 21, 2958-2966. 

Rodrtguez-Moreno, A., Herreras, O., and Lerma, J. (1997) Kainate receptors presynapti-cally downregulate GABAergic inhibition in the rat hippocampus. Neuron 19, 893-901... 

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

Durand GM, Kovalchuk Y, Konnerth A (1996) Long-term potentiation and fimctional synapse induction in developing hippocampus. Nature 381 71-75 Eder M, Becker K, Rammes G, et al (2003) Distribution and properties of functional postsy-naptic kainate receptors on neocortical layer V pyramidal neurons. J Nemosci 23 6660-... 

Regional distribution studies indicate that the highest density of kainate receptor occurs in the stratum lucidum of the hippocampus (mossy fiber system) and in the inner and outer layers of the neocortex. The highest density of NMDA receptors is found in the hippocampus, stratum radiatum, and in the striatum, thalamus, and cerebral cortex. The distribution of AMPA receptors is similar to that of NMDA receptors, but in the cerebellum AMPA receptors predominate in the molecular layer... 

Bertolino M., Baraldi M., Parenti C., Braghiroli D., DiBella M., Vicini S., and Costa E. (1993). Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus. Receptors Channels 1 267-278. 

Presynaptic kainate receptors have also been reported to control GABA release and to mediate opposing effects. In the hippocampus, spontaneous and evoked... 

Contractor A, Swanson GT, Sailer A, O Gorman S, Heinemann SF (2000) Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. J Neurosci 20 8269-78 Cossart R, Tyzio R, Dinocourt C, Esclapez M, Hirsch JC, Ben-Ari Y, Bernard C (2001) Presynaptic kainate receptors that enhance the release of GABA on CA1 hippocampal intemeurons. Neuron 29 497... 

Rodriguez-Moreno A, Lopez-Garcia JC, Lerma J (2000) Two populations of kainate receptors with separate signaling mechanisms in hippocampal intemeurons. PNAS 97 1293-8 Rodriguez-Moreno A, Sihra TS (2004) Presynaptic kainate receptor facilitation of glutamate release involves protein kinase A in the rat hippocampus. J Physiol (Lond) 557 733—45 Rogers M, Dani JA (1995) Comparison of quantitative calcium flux through NMDA, ATP, and ACh receptor channels. Biophys J 68 501-6... 

Scanziani M, Capogna M, Gahwiler BH, Thompson SM (1992) Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron 9 919-27 Schlicker E, Gothert M (1998) Interactions between the presynaptic alpha2-autoreceptor and presynaptic inhibitory heteroreceptors on noradrenergic neurones. Brain Res Bull 47 129-32. Schmitz D, Mellor J, Nicoll RA (2001) Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science 291 1972-6 Schneggenburger R, Neher E (2005) Presynaptic calcium and control of vesicle fusion. Curr Opin Neurobiol 15 266-74... 

Porter RH, Eastwood SL, Harrison PJ. 1997. Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Brain Res 751 217-231. 

Rodriguez-Moreno A. 2006. The role of kainate receptors in the regulation of excitatory synaptic transmission in the hippocampus. Rev Neurol 42 282-287. 

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