Neurochemical transmission in central synapses provides the brain with diverse strategies to modify communication between neurons. Classically, neurotransmitters such as the amino acids glutamate and GABA, are secreted in a regulated way in specific regions inside nerve terminals in order to exert their local and fast action on post synaptic neurons.
Figure 1 In purified nerve terminals, regular co-localization of morphologically different vesicles, i.e. small lucent and larger dense-cored, can be observed in electronmicroscopical studies (A)
Short K-depolarization pulses of 100 msec caused translocation of small vesicles towards the active zone (B)
In accordance with this morphometric differentiation, secretion of the small vesicle amino acid transmitters glutamate and GABA was much faster than that of the dense-cored vesicle neuropeptide Cholecystokinin (CCK) (C).
whereas a K-stimulation of 1 sec is required to get fusion of large-dense cored vesicles (D)
Previous studies were focussed on the regulation of transmitter release using brain (hippocampus) slices and purified nerve terminals. In animals which were made epileptic by kindling, a transient increase in GABA release in Hippocampus CA1 region upon electrical stimulation of Schaffer Collateral afferents was observed, which was closely associated with impairment of presynaptic GABA-B autoregulatory receptors. In purified nerve terminals a clear differentiation in activity-dependent trafficking of co-localized morphological different vesicles was observed, which closely resembled the secretion of the different transmitters stored in these vesicles. (see figures)
Current studies indicate that selective stimulation of the presynaptic GABA transporter regulates GABA secretion from diverse pools. A fast secretion from a Ca-dependent, vesicular pool, by depolarization via transporter-associated Na-entry, and a slower secretion from a cytosolic pool via transporter reversal. This latter mechanism provides the terminals to perform cross-talk with neighbouring nerve terminals.
The future direction of our studies will focus on the functional relevance of the neurochemical differentiation in synaptic transmission. For that purpose, studies will be performed in the ventral striatum where dense co-localization of GABA with either Met-enkephalin or Dynorphin does occur in functionally different Medium Spiny neurons. The contribution of these diverse transmitters to local transmission between synapses upon different stimulation patterns and their interference will be investigated.
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A presynaptic N-methyl-D-aspartate autoreceptor in rat hippocampus modulating amino acid release from a cytoplasmic pool.
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Activity-dependent neurotransmitter release kinetics: correlation with changes in morphological distributions of small and large vesicles in central nerve terminals.
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Regulation of cholecystokinin release from central nerve terminals.
Peptides 22, 1213-1221 (review).
Leenders, AGM, Lopes da Silva, FH, Ghijsen, WEJM and Verhage, M (2001)
Rab3a is involved in the transport of synaptic vesicles to the active zone in mouse brain nerve terminals.
Mol.Biol. Cell. 12, 3095-3102.
Leenders, AGM, Scholten, G, de Lange, RPJ, Lopes da Silva, FH and Ghijsen, WEJM (2002)
Sequential changes in synaptic vesicle pools and endosome-like organelles during depolarization near the active zone of central nerve terminals.
Neuroscience 109, 195-206.
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Neurotransmitter release from tottering mice nerve terminals with reduced expression of mutated P-, Q-type Ca2+-channels.
Eur. J. Neurosci. 15, 13-18
Ghijsen, WEJM, Leenders, AGM and Lopes da Silva, FH (2003)
Regulation of vesicle traffic and neurotransmitter release in isolated nerve terminals.
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Role of RabGTPases in the evolution of exocytotic membrane trafficking in eukaryotes.
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Ghijsen, WEJM and Leenders, AGM (2005)
Differential signaling in presynaptic transmitter release.
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This page was last updated on 5 nov 2010