Kainate receptor‐mediated depression of glutamatergic transmission involving protein kinase A in the lateral amygdala

Abstract

The amygdala is a component of the limbic system that is involved in emotional modulation of behaviour and learning and memory (LeDoux 2000). This structure is central for the acquisition, storage, and expression of conditioned fear memory (Lavond et al. 1993;LeDoux 1996;Davis 1997;McKernan and Shinnick-Gallagher 1997;Rogan et al. 1997;Fendt and Fanselow 1999). Synaptic inputs to the lateral nucleus of the amygdala (LA) from the thalamic medial geniculate nucleus (MGN) and from the auditory cortex are essential for the acquisition of this conditioning (LeDoux et al. 1990a;Romanski and LeDoux 1992;Campeau and Davis 1995). Synaptic transmission in the MGN to LA, is mediated by NMDA and non-NMDA receptors (Li et al. 1996;Weisskopf and LeDoux 1999;Zinebi et al. 2001).Kainate receptors are a family of glutamate receptors that can (postsynaptically) mediate synaptic transmission at some synapses, and (presynaptically) modulate transmitter release (see Rodríguez-Moreno and Sihra 2007a;Jane et al. 2009).In the modulatory context, kainate receptors have been implicated in the modulation of both glutamate and GABA release (see Rodríguez-Moreno and Sihra 2007a,b; Jane Received August 11, 2011; revised manuscript received January 11, 2012; accepted January 11, 2012.Address for correspondence and reprint requests to Dr Antonio Rodríguez-Moreno, Laboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cellular Biology, University Pablo de Olavide, Ctra. de Utrera, Km. 1, 41013, Sevilla, Spain. E-mail: arodmor@upo.es Abbreviations used: AMPA, a-amino-3-hydroxy-5-methylisoxazole-4-propionate; ATPA, (RS)-2-amino-3(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid; BAPTA, 1,2-bis(o-aminophenoxy)ethane-N,N,N¢, N¢-tetraacetic acid; CV, coefficient of variation; DPCPX, 8-cyclopentyl-1,3-dipropyl-7H-purine-2,6-dione; eEPSCs, evoked excitatory postsynaptic currents; KAR, kainate receptor; LA, lateral nucleus of the amygdala; LTP, long-term potentiation; MGN, medial geniculate nucleus; NBQX, 2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide; PKA, protein kinase A; PKC, protein kinase C; PPR, pair pulse ratio. MéxicoAbstract Kainate receptors (KARs) have been described as modulators of synaptic transmission at different synapses. However, this role of KARs has not been well characterized in the amygdala. We have explored the effect of kainate receptor activation at the synapse established between fibers originating at medial geniculate nucleus and the principal cells in the lateral amygdala. We have observed an inhibition of evoked excitatory postsynaptic currents (eEPSCs) amplitude after a brief application of KARs agonists KA and ATPA. Paired-pulse recordings showed a clear pair pulse facilitation that was enhanced after KA or ATPA application. When postsynaptic cells were loaded with BAPTA, the depression of eEPSC amplitude observed after the perfusion of KAR agonists was not prevented. We have also observed that the inhibition of the eEPSCs by KARs agonists was prevented by pro...

Kainate Receptors Modulating Glutamate Release in the Cerebellum

“…Biophysical studies with single-channel recording have shown GluK1 activity [85], suggesting these KARs are Ca 2+ permeable. A biphasic action of KARs, activated by the agonist domoate, has been shown previously at PF-PuC synapse, with low agonist concentrations, facilitating synaptic transmission and higher concentrations depressing synaptic transmission [86] in agreement with what has been found in the hippocampus [87][88][89], cortex [90], amygdala [91], and the thalamus [92]. EPSC trial-to-trial fluctuation analysis, failure rates, as well as paired-pulse ratios have shown that these facilitatory and depressive actions of KARs in the cerebellum are mediated by presynaptic KARs [80].…”

“…Kainate Receptors Modulating Glutamate Release in the Cerebellum DOI: http://dx.doi.org /10.5772/intechopen.87984 was observed as reported for other different brain areas including thalamus, cortex, hippocampus, and amygdala [89][90][91][92]. This depression of glutamate release was prevented in the presence of cAMP-RP (which inhibits the activation of PKA), but was not affected by any other experimental modification discussed above with respect to the facilitation of glutamate release.…”

Non-canonical Mechanisms of Presynaptic Kainate Receptors Controlling Glutamate Release

“…As in the hippocampus, facilitatory (Shin et al, 2010 ) and inhibitory (Negrete-Díaz et al, 2012 ) effects on glutamate release mediated by KAR activation have been described. A presynaptic AC/cAMP/PKA cascade mediating the depression of glutamate release through activation of presynaptic KARs has been shown at medial geniculate nucleus (MGN)-amygdala nucleus (LA) synapses (Negrete-Díaz et al, 2012 ). The effect was prevented by block of cAMP/PKA signaling by both Rp-Br-cAMP and H-89, but not by calphostin C inhibition of PKC.…”

“…Similarly, biphasic modulation is also evident in the modulation of glutamate release by KARs. Thus, KARs invoke both inhibitory effects (Vignes et al, 1998 ; Contractor et al, 2000 , 2003 ; Kamiya and Ozawa, 2000 ; Schmitz et al, 2000 ; Negrete-Díaz et al, 2006 , 2007 , 2012 ; Lyon et al, 2011 ), and facilitatory modulation of glutamate release (Bortolotto et al, 1999 ; Contractor et al, 2001 , 2003 ; Lauri et al, 2001a , b ; Breustedt and Schmitz, 2004 ; Rodríguez-Moreno and Sihra, 2004 , 2013 ; Pinheiro et al, 2007 ; Scott et al, 2008 ; Fernandes et al, 2009 ; Andrade-Talavera et al, 2012 , 2013 ).…”

Cortical kainate receptors and behavioral anxiety

“…In vitro slice recording showed that GluK1 is selectively expressed in interneurons, and its activation could largely depolarize those interneurons and increase synaptic GABA release as well as GABA tonic currents. More importantly, the GluK1 activation in the basolateral amygdala reduced the output to the central amygdala, which may explain the increased anxiety phenotype in the GluK1 knockout mice [6] In addition, the regulation of excitatory glutamate transmission by KA receptors have been also reported in the amygdala [30, 31], and such regulation is also mixed (inhibition and facilitation).…”