Régulation du cycle vésiculaire et de l’approvisionnement en GABA des interneurones de l’hippocampe en fonction de l’activité

Abstract : In the hippocampus, GABAergic interneurons represent only 10% of the neuronal population but are able to synchronize the activity of large neuronal networks. They compensate their numerical inferiority by a large axonal arborization to sustain synaptic activity at high frequency and adjust the balance between excitation and inhibition for different regime of activity. Since small central synapses contain a limited pool of vesicles, their recycling by endocytosis is essential to maintain transmission during repeated activity. The filling of recycling vesicles with GABA is dependent on its supply in terminals which should be adjusted to the demand imposed by vesicular recycling. Our results reveal new transporter mechanisms that adapt GABA supply to neuron activity, suggesting a direct coupling between the neurotransmitter and the vesicle cycles. We show that high recycling activity increases GABA supply, probably by increasing the number of glutamine transporters at the membrane. By developing and using FM5-95 and VGAT-pHluorin with a new experimental paradigm, we provide evidence for a metabolic regulation of the vesicle cycle that involves a dynamic adaptation of the recycling pool to the neurotransmitter availability. The nature of the sensor of this regulation and its cytosolic or luminal location remain to be determined.
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Laurine Bonet. Régulation du cycle vésiculaire et de l’approvisionnement en GABA des interneurones de l’hippocampe en fonction de l’activité. Neurosciences [q-bio.NC]. PSL Research University, 2016. Français. ⟨NNT : 2016PSLEE027⟩. ⟨tel-02275629⟩

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