In the intact developing neocortex in vivo, GABA acts as a mainly depolarizing neurotransmitter. The objective of the present proposal is to explore to which extent depolarizing GABA actions in immature cortical neurons contribute to the activity-dependent construction of the mouse primary visual cortex. Based on novel experimental findings as well as mouse models and analytical tools developed during the first funding period, we will explore how depolarizing GABA actions I) orchestrate the generation of patterned network activity in vivo, II) impact the development of visual feature representations and III) affect sensory-dependent learning in the visual neocortex. We will address these questions in an interdisciplinary approach combining expertise from the fields of genetics, physiology and computational neuroscience. Firstly, we will manipulate intraneuronal chloride homeostasis in a cell type- and time-specific manner. Secondly, we will apply two-photon Ca2+ imaging and electrophysiological techniques to record spontaneous and visually evoked neuronal network activity at single-cell resolution in the intact brain. In addition, behavioural testing paradigms will be used in order to link potential alterations at the microscopic level to changes in sensory-dependent behaviours. Thirdly, we will develop data-driven computational network models in order to gain a deeper mechanistic understanding of the observed spatiotemporal dynamics of neuronal network activity during development. Collectively, the complementarity of the developed approaches will be crucial to identify potential causal functions of depolarizing GABAergic transmission for the activity-dependent refinement of the visual neocortex.
DFG Programme
Priority Programmes
