Electrically evoked GABA release in rat hippocampus CA1 region and its changes during kindling epileptogenesis.

Previous findings on changes in K+-induced GABA release from hippocampal slices during kindling epileptogenesis were reinvestigated using physiological electrical stimulation. For that purpose, a procedure was developed enabling neurochemical monitoring of GABA release locally in the CA1 region of rat hippocampal slices upon tetanic stimulation of Schaffer-collateral fibers. In the presence of a GABA reuptake blocker, subsequent application of short (3 s) pulses of 50-Hz stimuli induced a local transient increase in GABA release.

Differential signaling in presynaptic neurotransmitter release.

Neuronal communication is tightly regulated by presynaptic signaling, thereby temporarily and locally secreting one or more transmitters in order to exert propagation or modulation of network activity. In the last 2 decades our insight into the molecular regulation of presynaptic transmitter vesicle traffic and fusion has exponentionally grown due to the identification of specific functional interactions between presynaptic proteins involved in these processes. In addition, a plethora of extracellular and intracellular messengers regulate neurotransmitter release, occasionally leading to short- or long-term adaptations of the synapse to altered environmental signals.

Regulation of vesicle traffic and neurotransmitter release in isolated nerve terminals.

In this overview current insights in the regulation of presynaptic transmitter release, mainly acquired in studies using isolated CNS nerve terminals are highlighted. The following aspects are described. (i) The usefulness of pinched-off nerve terminals, so-called synaptosomes, for biochemical and ultrastructural studies of presynaptic stimulus-secretion coupling.

Neurotransmitter release from tottering mice nerve terminals with reduced expression of mutated P- and Q-type Ca2+-channels.

Neurotransmitter release is triggered by Ca2+-influx through multiple sub-types of high voltage-activated Ca2+-channels. Tottering mice have a mutation in the alpha1A pore-forming subunit of P- and Q-type Ca2+-channels, two prominent sub-types that regulate transmitter release from central nerve terminals. Immunoblotting analysis of purified forebrain terminals from tottering mice revealed an 85% reduction in the protein expression level of the mutated alpha1A subunit compared to expression of the alpha1A subunit in wild-type terminals.

Glutamate transporters alterations in the reorganizing dentate gyrus are associated with progressive seizure activity in chronic epileptic rats.

The expression of glial and neuronal glutamate transporter proteins was investigated in the hippocampal region at different time points after electrically induced status epilepticus (SE) in the rat. This experimental rat model for mesial temporal lobe epilepsy is characterized by cell loss, gliosis, synaptic reorganization, and chronic seizures after a latent period. Despite extensive gliosis, immunocytochemistry revealed only an up-regulation of both glial transporters localized at the outer aspect of the inner molecular layer (iml) in chronic epileptic rats.

A biochemical approach to study sub-second endogenous release of diverse neurotransmitters from central nerve terminals.

Exocytosis in central nerve terminals is rapidly triggered by the influx of calcium through high voltage sensitive Ca2+ -channels. Mainly due to their small size, studies in which neurotransmitter release from these terminals was determined at the sub-second time-scale are still rather limited. Here we describe the use of a pneumatic rapid mixing device, allowing application of short (> or = 50 ms) K+ -depolarizing pulses to purified nerve terminals, synaptosomes, to trigger endogenous release of different transmitter types.