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Synaptic input mapping during cortical map plasticity

Project description

Lighting the way to somatosensory synaptic plasticity

The human brain exhibits tremendous plasticity or capacity for change manifested in numerous biophysical ways and subserving processes from memory to recovery after trauma. Synaptic plasticity, changes in the connections between neurons, is often the result of altered input from presynaptic neurons creating long-term altered responses in post-synaptic neurons. Understanding of this process is enhanced with animal models. With the support of the Marie Skłodowska-Curie Actions programme, the iMAC project is investigating synaptic plasticity in the rat somatosensory cortex following whisker trimming. Specifically, the team is using optical methods to evaluate the mechanisms of augmented excitatory phenomena in post-synaptic cells of the cortex that are related to descending presynaptic inputs from higher order cells.

Objective

The rodent primary somatosensory cortex (S1) contains a malleable topographic map, in which cortical columns functionally represent individual facial whiskers. When all whiskers but two are trimmed, the cortical representations of the two spared whiskers partially fuse. This fusion is associated and possibly facilitated by an increase in NMDAR-mediated dendritic nonlinearities (plateau potentials) in L2/3 neurons, which are dependent on inputs from the higher-order posteromedial thalamic complex (POm). It has been shown that plateau potentials generated by these inputs can promote plasticity of sensory-related synaptic inputs. However, the spatiotemporal relationships between the plateau potential-generating POm and the sensory-related synaptic inputs on L2/3 neurons, and possible rearrangements therein during plasticity, are not understood.
Recently developed genetically encoded glutamate indicators (GEGIs), which the fellow was involved in, have enabled the visualization of active excitatory inputs. Here, the fellow proposes a novel methodology (iMAC, Input Mapping of Active Connections), where she combines two state-of-the-art optogenetics and optophysiology tools. A presynaptic light-sensitive opsin will allow optical activation of ascending POm inputs, while a postsynaptic GEGI will allow the visualization, i.e. mapping of the activated synapses on L2/3 pyramidal neurons. First, the fellow will establish a proto-map of these higher-order thalamocortical excitatory inputs in an ex vivo preparation, followed by a proof of principle in vivo in the awake mouse. Second, the fellow will compare the POm-driven synaptic maps with those recruited by whisker sensory stimulation in vivo. Third, she will determine how these rearrange upon sensory deprivation.
Altogether, this work will investigate the spatiotemporal relationships between POm and sensory-driven inputs onto L2/3 neurons and reveal possible rearrangements therein related to cortical map plasticity.

Coordinator

UNIVERSITE DE GENEVE
Net EU contribution
€ 191 149,44
Address
RUE DU GENERAL DUFOUR 24
1211 Geneve
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Genève
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 191 149,44