Differential cAMP Signaling at Hippocampal Output Synapses

Wozny, Christian; Maier, Nikolaus; Fidzinski, Pawel; Breustedt, Jörg; Behr, Jüergen; Schmitz, Dietmar

doi:10.1523/jneurosci.4973-08.2008

Cited by 33 publications

(29 citation statements)

References 43 publications

(57 reference statements)

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“…In control tissue, subicular LTP is NMDAR-dependent (Aoto et al, 2013;Wozny et al, 2008aWozny et al, , 2008b. In MK-801-treated rats, we found a presynaptic late-onset LTP restricted to subicular pyramidal cells.…”

Section: Discussionmentioning

confidence: 56%

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Bartsch

Fidzinski

Huck

et al. 2014

Neuropsychopharmacol

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Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca 2 þ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system. Neuropsychopharmacology (2015) 40, 987-995;

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Section: Discussionmentioning

confidence: 56%

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Bartsch

Fidzinski

Huck

et al. 2014

Neuropsychopharmacol

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“…In regular-firing neurons of the subiculum, LTP is induced by postsynaptic activation of NMDARs, whereas in burst-firing neurons LTP is induced by presynaptic activation of PKA (Wozny et al, 2008; Behr et al, 2009). We asked whether LTP may also be differentially affected by the presynaptic β-neurexin KO in regular- and burst-firing neurons similar to endocannabinoid signaling.…”

Section: Resultsmentioning

confidence: 99%

“…Presynaptic LTP in burst-firing neurons depends on adenylate cyclase/PKA signaling (Wozny et al, 2008). Interestingly, CB1Rs are coupled to Gαi which inhibits adenylate cyclase (Castillo et al, 2012; Kano et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling

Anderson

Aoto

Tabuchi

et al. 2015

Cell

136

173

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α- and β-neurexins are presynaptic cell-adhesion molecules implicated in autism and schizophrenia. We find that although β-neurexins are expressed at much lower levels than α-neurexins, conditional knockout of β-neurexins with continued expression of α-neurexins dramatically decreased neurotransmitter release at excitatory synapses in cultured cortical neurons. The β-neurexin knockout phenotype was attenuated by CB1-receptor inhibition which blocks presynaptic endocannabinoid signaling or by 2-arachidonoylglycerol synthesis inhibition which impairs postsynaptic endocannabinoid release. In synapses formed by CA1-region pyramidal neurons onto burst-firing subiculum neurons, presynaptic in vivo knockout of β-neurexins aggravated endocannabinoid-mediated inhibition of synaptic transmission and blocked LTP; presynaptic CB1-receptor antagonists or postsynaptic 2-arachidonoylglycerol synthesis inhibition again reversed this block. Moreover, conditional knockout of β-neurexins in CA1-region neurons impaired contextual fear memories. Thus, our data suggest that presynaptic β-neurexins control synaptic strength in excitatory synapses by regulating postsynaptic 2-arachidonoylglycerol synthesis, revealing an unexpected role for β-neurexins in the endocannabinoid-dependent regulation of neural circuits.

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“…Staurosporine inhibits a variety of protein kinases including protein kinase C (39,40). H-89 targets protein kinase A (PKA) (41,42) but also inhibits many other protein kinases (43). The lack of inhibition by these two inhibitors strengthens the hypothesis that Src kinases play a central role in the ␤-ionone-activated signaling pathway.…”

Section: Psgr Activation Triggers Opening Of a Plasma Membranementioning

confidence: 91%

G Protein-coupled Receptor Signaling via Src Kinase Induces Endogenous Human Transient Receptor Potential Vanilloid Type 6 (TRPV6) Channel Activation

Spehr

Gelis

Osterloh

et al. 2011

Journal of Biological Chemistry

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Ca2؉ homeostasis plays a critical role in a variety of cellular processes. We showed previously that stimulation of the prostate-specific G protein-coupled receptor (PSGR) enhances cytosolic Ca 2؉ and inhibits proliferation of prostate cells. Here, we analyzed the signaling mechanisms underlying the PSGR-mediated Ca 2؉ increase. Using complementary molecular, biochemical, electrophysiological, and live-cell imaging techniques, we found that endogenous Ca 2؉ -selective transient receptor potential vanilloid type 6 (TRPV6) channels are critically involved in the PSGR-induced Ca 2؉ signal. Biophysical characterization of the current activated by PSGR stimulation revealed characteristic properties of TRPV6. The molecular identity of the involved channel was confirmed using RNA interference targeting TrpV6. TRPV6-mediated Ca 2؉ influx depended on Src kinase activity. Src kinase activation occurred independently of G protein activation, presumably by direct interaction with PSGR. Taken together, we report that endogenous TRPV6 channels are activated downstream of a G protein-coupled receptor and present the first physiological characterization of these channels in situ. Ca2ϩ ions function as ubiquitous second messengers that control a variety of cellular processes such as differentiation, proliferation, and apoptosis (1). Epithelial cells control their cytosolic Ca 2ϩ level via non-voltage-gated plasma membrane cationic channels and/or depletion of intracellular Ca 2ϩ stores followed by Ca 2ϩ entry via store-operated channels. Several plasma membrane channels have been implicated in modulation of cytosolic Ca 2ϩ in prostate epithelial cells (2-6). Notably, the two highly Ca 2ϩ -selective Ca 2ϩ (re)absorption channels TRPV5 3 and TRPV6 were found to be expressed in prostate cells (7-9). TRPV6 has been proposed to play a role in prostate cancer cell proliferation (9, 10). The biophysical characteristics of recombinantly overexpressed TRPV6 channels have been studied intensively (11). However, no information on channel physiology in native cells is available. Overexpression of TRPV6 leads to constitutively open channels, and so far no activation mechanism has been described (12). We previously reported that activation of PSGR by ␤-ionone induces an increase in cytosolic Ca 2ϩ and a decreased proliferation rate of prostate cancer cells (13). Thus, the aim of the present study was to examine the mechanism of Ca 2ϩ entry into prostate epithelial cells upon stimulation of PSGR, a class A GPCR that was initially identified as a prostate-specific tumor biomarker (14). Here, we identified TRPV6 as an important signaling protein downstream of activated PSGR showing that TRPV6 can function as a receptor-operated channel. We further identified the tyrosine kinase Src as a signaling protein coupling PSGR and TRPV6 independently of G proteins. In this context, we present the first electrophysiological analysis of endogenous TRPV6 channels. EXPERIMENTAL PROCEDURESCell Culture and Transfection-LNCaP cells were maintained in RPMI 1640...

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Differential cAMP Signaling at Hippocampal Output Synapses

Cited by 33 publications

References 43 publications

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling

G Protein-coupled Receptor Signaling via Src Kinase Induces Endogenous Human Transient Receptor Potential Vanilloid Type 6 (TRPV6) Channel Activation

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