Zinc enhances long-term potentiation through P2X receptor modulation in the hippocampal CA1 region

Lorca, Ramón A.; Rozas, Carlos; Loyola, Sebastián; Moreira-Ramos, Sandra; Zeise, Marc L.; Kirkwood, Alfredo; Huidobro‐Toro, J. Pablo; Morales, Bernardo

doi:10.1111/j.1460-9568.2010.07589.x

Cited by 42 publications

(36 citation statements)

References 46 publications

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“…Of the seven P2X subunits characterized to date (named P2 Â 1 through P2 Â 7), P2X4 receptors (P2X4Rs) are the most abundant in the central nervous system (Buell et al, 1996;Soto et al, 1996), and are expressed in neurons across multiple regions of the brain and spinal cord, as well as in microglia (Burnstock and Knight, 2004;Ulmann et al, 2008). Recent studies have pointed to the implication of P2X4 in the regulation of multiple nervous functions, including neuropathic pain (Tsuda et al, 2003;Ulmann et al, 2008), neuroendocrine functions (Zemkova et al, 2010), and hippocampal plasticity (Baxter et al, 2011;Lorca et al, 2011;Sim et al, 2006). In addition, P2X4 receptors have been recently shown to modulate the function of other major ionotropic targets, such as N-methyl-D-aspartate (NMDA) glutamate receptors (Baxter et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice

Wyatt

Godar

Khoja

et al. 2013

Neuropsychopharmacol

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Purinergic P2X receptors are a family of ligand-gated ion channels gated by extracellular adenosine 5'-triphosphate (ATP). Of the seven P2X subtypes, P2X4 receptors (P2X4Rs) are richly expressed in the brain, yet their role in behavioral organization remains poorly understood. In this study, we examined the behavioral responses of P2X4R heterozygous (HZ) and knockout (KO) mice in a variety of testing paradigms designed to assess complementary aspects of sensory functions, emotional reactivity, and cognitive organization. P2X4R deficiency did not induce significant alterations of locomotor activity and anxiety-related indices in the novel open field and elevated plus-maze tests. Conversely, P2X4R KO mice displayed marked deficits in acoustic startle reflex amplitude, as well as significant sensorimotor gating impairments, as assessed by the prepulse inhibition of the startle. In addition, P2X4R KO mice displayed enhanced tactile sensitivity, as signified by a lower latency in the sticky-tape removal test. Moreover, both P2X4R HZ and KO mice showed significant reductions in social interaction and maternal separation-induced ultrasonic vocalizations in pups. Notably, brain regions of P2X4R KO mice exhibited significant brain-regional alterations in the subunit composition of glutamate ionotropic receptors. These results collectively document that P2X4-deficient mice exhibit a spectrum of phenotypic abnormalities partially akin to those observed in other murine models of autism-spectrum disorder. In conclusion, our findings highlight a putative role of P2X4Rs in the regulation of perceptual and sociocommunicative functions and point to these receptors as putative targets for disturbances associated with neurodevelopmental disorders.

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Section: Introductionmentioning

confidence: 99%

Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice

Wyatt

Godar

Khoja

et al. 2013

Neuropsychopharmacol

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“…Most previous studies suggested zinc attenuated LTP in mossy fibers, 35 but another study showed LTP was enhanced by zinc in the hippocampal CA1 region. 36 Recently, Izumi et al found zinc induction of LTP at low micromolar concentrations, while attenuating it at high micromolar concentrations. Homeostasis of synaptic zinc is critical for LTP induction.…”

Section: Effects Of Nano-zno On Ltp and Depotentiationmentioning

confidence: 99%

Nano-zinc oxide damages spatial cognition capability via over-enhanced long-term potentiation in hippocamus of Wistar rats

Han¹,

Tian²,

Zhang³

et al. 2011

IJN

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This study focused on the effects of zinc oxide nanoparticles (nano-ZnO) on spatial learning and memory and synaptic plasticity in the hippocampus of young rats, and tried to interpret the underlying mechanism. Rats were randomly divided into four groups. Nano-ZnO and phosphate-buffered saline were administered in 4-week-old rats for 8 weeks. Subsequently, performance in Morris water maze (MWM) was determined, and then long-term potentiation (LTP) and depotentiation were measured in the perforant pathway to dentate gyrus (DG) in anesthetized rats. The data showed that, (1) in MWM, the escape latency was prolonged in the nano-ZnO group and, (2) LTP was significantly enhanced in the nano-ZnO group, while depotentiation was barely influenced in the DG region of the nano-ZnO group. This bidirectional effect on long-term synaptic plasticity broke the balance between stability and flexibility of cognition. The spatial learning and memory ability was attenuated by the alteration of synaptic plasticity in nano-ZnO-treated rats.

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“…This effect is mediated by a direct action via P2XRs on SBCs, which evoke membrane depolarization and calcium transients (Milenkovic et al, 2009). By increasing [Ca 2ϩ ] i , P2XRs can mediate long-term plasticity changes (long-term potentiation and long-term depression) in the CA1 pyramidal neurons of the hippocampus (Pankratov et al, 2002;Yamazaki et al, 2003;Lorca et al, 2011). Future experiments will have to clarify whether similar regulations of synaptic strength occur in developing bushy cells.…”

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confidence: 99%

Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem

Dietz

Jovanovic²,

Wielsch³

et al. 2012

Journal of Neuroscience

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In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca 2ϩ signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.

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Zinc enhances long-term potentiation through P2X receptor modulation in the hippocampal CA1 region

Cited by 42 publications

References 46 publications

Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice

Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice

Nano-zinc oxide damages spatial cognition capability via over-enhanced long-term potentiation in hippocamus of Wistar rats

Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem

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