Synaptic modulation NMDA receptors

Reports that AA is released primarily by G-protein-mediated PLA2 activation remain to be confirmed [84, 85]. In addition, modulation of PLA2 by Ca2+ and protein kinase needs to be better defined. It is clear that NMDA receptor activation promotes the release of AA [86], and that a variety of eicosanoids are then generated (Fig 33-2,33-3). The modulatory events that channel AA towards specific eicosanoids are not understood. The endocannabinoid family of lipid messengers will remain an active focus of interest because of the growing evidence of their actions in synaptic function, learning, memory, and other forms of behavior [56,87]. 

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). 

Barazangi N, Role LW (2001) Nicotine-induced enhancement of glutamatergic and GABAergic synaptic transmission in the mouse amygdala. J Neurophysiol 86 463-74 Bardoni R, Torsney C, Tong C-K, Prandini M, MacDermott AB (2004) Presynaptic NMDA receptors modulate glutamate release from primary sensory neurons in rat spinal cord dorsal horn. J Neurosci 24 2774-81... 

Initially, Gly was described to be restricted to the mammalian spinal cord, but subsequently it has been detected supraspinally as well (Legendre, 2001). Gly receptors (GlyRs) belong to the superfamily of receptor channels, which are generally composed of five subunits (al-4, P) (Webb and Lynch, 2007). The different a-and P-subunits are differently localized. The GlyR is a pentameric chloride channel, and it is classically known for mediating inhibitory synaptic transmission between interneurons and motor neurons in reflex circuits of the spinal cord, but they are also found presynaptically, where they modulate neurotransmitter release (Lynch, 2009 Webb and Lynch, 2007). The picture is complicated by the fact that Gly also binds to and activates NMDA receptors, therefore, it can influence the pain threshold by this action as well (see above. Section 2.3.1) (Zeilhofer, 2005). 

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