Rapid regulation of endoplasmic reticulum dynamics in dendritic spines by NMDA receptor activation.

Endoplasmic reticulum (ER) is motile within dendritic spines, but the mechanisms underlying its regulation are poorly understood. To address this issue, we have simultaneously imaged morphology and ER content of dendritic spines in cultured dissociated mouse hippocampal neurons. Over a 10 min period, spines were highly dynamic, with spines both increasing and decreasing in volume.

ACET is a highly potent and specific kainate receptor antagonist: characterisation and effects on hippocampal mossy fibre function.

Kainate receptors (KARs) are involved in both NMDA receptor-independent long-term potentiation (LTP) and synaptic facilitation at mossy fibre synapses in the CA3 region of the hippocampus. However, the identity of the KAR subtypes involved remains controversial. Here we used a highly potent and selective GluK1 (formerly GluR5) antagonist (ACET) to elucidate roles of GluK1-containing KARs in these synaptic processes.

The induction of long-term plasticity of non-synaptic, synchronized activity by the activation of group I mGluRs.

It is well established that activation of group I metabotropic glutamate receptors (mGluRs) produces long-lasting alterations in synaptic efficacy. We now demonstrate that activation of mGluRs can also induce long-term alterations in synchronised network activity that are both induced and expressed in the absence of chemical synaptic transmission. Specifically, in hippocampal slices in which synaptic transmission was eliminated by perfusing with a Ca2+-free medium, the selective group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced a persistent (>3h) enhancement (>2-fold) of the frequency of synchronised bursting activity.

The use of the hippocampal slice preparation in the study of Alzheimer's disease.

In the present article we show how studying synaptic mechanisms in hippocampal slice preparations provides information that may be useful in, firstly, the understanding of the aetiology of Alzheimer's disease and, secondly, in the development of novel therapies for dementia. We use several examples, drawn from our own work: (i) The identification of the function of AMPA receptors and NMDA receptors in synaptic transmission and synaptic plasticity. (ii) The discovery of mechanisms that can regulate the activation of NMDA receptors.

Promiscuous interactions between AMPA-Rs and MAGUKs.

What controls the number of AMPA receptors at excitatory synapses? MAGUKs are known to play a critical role in this process, but which ones are involved and when has been contentious. In this issue of Neuron, Elias et al. have elucidated the roles of three MAGUKs, PSD-95, PSD-93, and SAP-102, in the targeting of AMPA receptors to synapses in hippocampal neurons.