SyPoFaPIC · THE ROLE OF SYNAPSE POLARITY ON THE FORMATION AND PLASTICITY OF INHIBITORY CONNECTIONS

Линиите свързват координатора с партньорите.

Накратко на български

Цел на проекта

In adults, GABA acts as the primary inhibitory neurotransmitter, but during early development, GABAergic synaptic transmission has depolarising effects and can influence various developmental processes. The role of depolarising GABA in synapse formation remains unclear. Specifically, whether changes in intracellular chloride concentration influence synapse formation directly or whether it occurs concomitantly with it is not known. Moreover, the specifics of how and where this process unfolds across different subcellular compartments have not been studied.Our hypothesis posits that GABAergic synapse formation requires depolarising GABA. Subsequently, an increase in GABAergic transmission promotes the developmental switch in chloride levels, a progression that unfolds spatially and temporally along the dendritic-axonal axis within the cell.This proposal seeks to elucidate the fundamental mechanisms governing chloride balance and the formation of GABAergic synapses in living organisms. These developmental processes occur across various spatial dimensions with precise timing. The strength of this proposal lies in integrating cutting-edge methodologies to comprehensively describe both the structure and function of the dynamic chloride environment within developing neurons and its impact on the formation, function, and plasticity of inhibitory synapses in vivo. This will be accomplished by implementing an in vivo two-photon chloride imaging approach, together with precise tracing of inhibitory synapse formation over development and following manipulations of either intracellular chloride levels or neuronal network activity.Disruptions in inhibitory synapses and changes in the timing of the postnatal intracellular chloride shift have been associated with developmental brain disorders. Hence, gaining insights into the principles governing GABAergic synaptogenesis and synapse plasticity will contribute to a better understanding of these pathological mechanisms.

Оригинален текст от CORDIS (на английски).

Участници

• KING'S COLLEGE LONDON · LondonКоординаторОбединеното кралство

Връзки

• Виж в CORDIS
• DOI: 10.3030/101209522
• https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e52d8dbe0f&appId=PPGMS