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Presenilin mutations result in exaggerated endoplasmic reticulum (ER) calcium release in cellular and animal models of Alzheimer's disease (AD). In this study, we examined whether dysregulated ER calcium release in young 3xTg-AD neurons alters synaptic transmission and plasticity mechanisms before the onset of histopathology and cognitive deficits. Using(More)
Activity-dependent plasticity is a fundamental feature of most CNS synapses and is thought to be a synaptic correlate of memory in rodents. In humans, NMDA receptors have been linked to verbal memory processes, but it is unclear whether NMDA receptor-dependent synaptic plasticity can be recruited for information storage in the human CNS. Here we have for(More)
Deficits in synaptic function, particularly through NMDA receptors (NMDARs), are linked to late-stage cognitive impairments in Alzheimer's disease (AD). At earlier disease stages, however, there is evidence for altered endoplasmic reticulum (ER) calcium signaling in human cases and in neurons from AD mouse models. Despite the fundamental importance of(More)
Arachidonic acid metabolites have been proposed as signaling molecules in hippocampal long-term potentiation (LTP) and long-term depression (LTD) for >15 years. However, the functional role of these molecules remains controversial. Here we used a multidisciplinary biochemical, electrophysiological, and genetic approach to examine the function of the(More)
A significant fraction of the total calciumcalmodulin-dependent protein kinase II (CaMKII) activity in neurons is associated with synaptic connections and is present in nerve terminals, thus suggesting a role for CaMKII in neurotransmitter release. To determine whether CaMKII regulates neurotransmitter release, we generated and analyzed knockout mice in(More)
Activity-dependent synaptic plasticity is a fundamental feature of CNS synapses. Intriguingly, the capacity of synapses to express plastic changes is itself subject to considerable activity-dependent variation, or metaplasticity. These forms of higher order plasticity are important because they may be crucial to maintain synapses within a dynamic functional(More)
Deficits in synaptic function, particularly through NMDA receptors (NMDARs), are linked to late-stage cognitive impairments in Alzhei-mer's disease (AD). At earlier disease stages, however, there is evidence for altered endoplasmic reticulum (ER) calcium signaling in human cases and in neurons from AD mouse models. Despite the fundamental importance of(More)
Alzheimer's disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic(More)
We previously showed that the time-dependent intensification ("incubation") of cue-induced cocaine seeking after withdrawal from extended-access cocaine self-administration is accompanied by accumulation of Ca(2+)-permeable AMPA receptors (CP-AMPARs) in the rat nucleus accumbens (NAc). These results suggest an enduring change in Ca(2+) signaling in NAc(More)
The amygdala plays key roles in several aspects of addiction to drugs of abuse. This brain structure has been implicated in behaviours that reflect drug reward, drug seeking, and the aversive effects of drug withdrawal. Using a model that involves repeated cocaine injections to approximate 'binge' intoxication, we show in rats that during cocaine(More)