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Enrico Cherubini Dynamics of GABA release at mossy fibre-CA3 synapses in the immature rat hippocampus.

Abstract :


I
n the adult rat hippocampus, granule cell mossy fibers (MFs) form excitatory glutamatergic synapses with CA3 principal cells and local inhibitory interneurons. However, evidence has been provided that in young animals and after seizures the same fibers can release in addition to glutamate GABA. Here we show that, during the first postnatal week, stimulation of granule cells in the dentate gyrus gave rise to monosynaptic GABAA-mediated responses in principal cells and in interneurons.
These synapses were indeed made by MFs since they exhibited strong paired-pulse facilitation, high sensitivity to the metabotropic glutamate receptor (mGluR) agonist L-AP4, short-term frequency-dependent facilitation. MF responses were potentiated by blocking the plasma membrane GABA transporter GAT-1 with NO-711 or by allosterically modulating GABAA receptors with flurazepam. Chemical stimulation of granule cells dendrites with glutamate induced barrages of GABAA-mediated postsynaptic currents into target neurons. Furthermore, immunocytochemical experiments demonstrated co-localization of VGAT with VGLUT1 and ZnT3, suggesting that GABA can be taken up and stored in synaptic vesicles of MF terminals.
Additional fibers releasing both glutamate and GABA into principal cells and interneurons were recruited by increasing the strength of stimulation. Both the GABAergic and the glutamatergic component of synaptic currents occurred with the same latency and were reversibly abolished by L-AP4 indicating that they originated from the MFs. GABAergic signaling may play a crucial role in tuning hippocampal network during postnatal development.
Low-threshold GABA-releasing fibers may undergo elimination and this may occur when GABA shifts from the depolarizing to the hyperpolarizing direction.

Selected publications

Safiulina VF, Kasyanov AM, Giniatullin R, Cherubini E.
Adenosine down-regulates giant depolarizing potentials in the developing rat hippocampus by exerting a negative control on glutamatergic inputs.
J Neurophysiol. 2005 Oct;94(4):2797-804.
Mohajerani MH, Cherubini E.
Spontaneous recurrent network activity in organotypic rat hippocampal slices.
Eur J Neurosci. 2005 Jul;22(1):107-18.

Christophe Mulle