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Séminaire impromptu - Katalin TothFunctional heterogeneity among vesicles in hippocampal mossy fibre terminals.

Abstract :

Readily releasable pool of synaptic vesicles is composed of vesicles with heterogeneous molecular and functional properties. Emerging evidence suggest that three modes of neurotransmitter release: synchronous, asynchronous and spontaneous utilize distinct release machineries and might preferentially involve vesicles with specific properties. Functionally heterogenous vesicles in the same presynaptic terminal are generated via different endocytotic pathways. Clathrin-dependent endocytosis utilizes adaptor protein AP-2 while bulk endocytosis leads to the transient formation of endosomes and it is dependent on adaptor protein AP-3. The exact role of vesicles derived through the two recycling pathways in various forms of neurotransmitter release remains largely unknown. 

We used AP-3 knockout mice (Ap3b2-/-) lacking bulk endosomal vesicle formation to explore the physiological role of the vesicular pool formed via this pathway in synapses between mossy fibre boutons and hippocampal CA3 pyramidal cells. We found that during asynchronous release a distinct pool of vesicles generated via bulk endocytosis is released. Asynchronous release rate was significantly reduced already after the 3rd stimuli in the train. Quantal parameters (p, Q and N), the size of the readily releasable pool and its recovery speed were comparable between WT and KO mice further underlining similar properties of synchronous neurotransmitter release.
We aimed to determine the consequences of diminished asynchronous release on synaptic information transfer. We analyzed the relationship between natural presynaptic stimulus pattern and postsynaptic action potential (AP) generation. In the absence of asynchronous release the probability of postsynaptic AP generation during natural spike trains was reduced and the variability of the postsynaptic responses was increased. These findings indicate that asynchronous release plays a crucial role in information coding, it is essential for optimal and reliable synaptic information transfer.


Selected publications

Raingo J, Khvotchev M, Liu P, Darios F, Li YC, Ramirez DM, Adachi M, Lemieux P, Toth K, Davletov B, Kavalali ET. (2012) VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission. Nature Neuroscience 

 Lavoie N. Jeyaraju DV, Peralta M, Seress L, Pellegrini L and Toth K (2011) Vesicular zinc regulates the Ca2+ sensitivity of a subpopulation of presynaptic vesciles in hippocampal mossy fiber terminals. J. Neuroscience 31:18251-65

 Evstratova A.  and Toth K. (2011) Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones. Journal of Physiology 589:5677-89

 Toth K. (2011) Zinc in neurotransmission. Annu Rev Nutr 31: 139-53

Scientific focus :

Cellular and Molecular Neuroscience

Structural and functional organization of the presynaptic terminal. The role of synaptic plasticity in spacial navigation.

-Basic principles of neurotransmitter release and synaptic plasticity
-Functional significance of a diverse vesicle pool
-Correlation between synaptic plasticity and exploratory behaviour