Asynchronous glutamate release is enhanced in low release efficacy synapses and dispersed across the active zone.

The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties of neuronal synapses and regulation of neuronal network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using the fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular release in tens to hundreds of individual synaptic outputs from single pyramidal cells with 4 millisecond temporal and 75 nm spatial resolution.

Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release.

Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca activation mechanism has been well-characterized, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerization provides the molecular basis for the Syt1 clamping function.

Behavior-dependent activity patterns of GABAergic long-range projecting neurons in the rat hippocampus.

Long-range glutamatergic and GABAergic projections participate in temporal coordination of neuronal activity in distributed cortical areas. In the hippocampus, GABAergic neurons project to the medial septum and retrohippocampal areas. Many GABAergic projection cells express somatostatin (SOM+) and, together with locally terminating SOM+ bistratified and O-LM cells, contribute to dendritic inhibition of pyramidal cells.

Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy.

Mutations in CACNA1A, which encodes the principal subunit of the P/Q calcium channel, underlie episodic ataxia type 2 (EA2). In addition, some patients with episodic ataxia complicated by epilepsy have been shown to harbour CACNA1A mutations, raising the possibility that P/Q channel dysfunction may be linked to human epilepsy. We undertook a review of all published CACNA1A EA2 cases and this showed that 7% have epilepsy--representing a sevenfold increased epilepsy risk compared to the background population risk (P<0.

At clinically relevant concentrations the anaesthetic/amnesic thiopental but not the anticonvulsant phenobarbital interferes with hippocampal sharp wave-ripple complexes.

Background: Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity.