Synaptic input mapping during cortical map plasticity: iMAC

Programme(s):

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions 
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Topic(s): MSCA-IF-2020 - Individual Fellowships

Call for proposal: H2020-MSCA-IF-2020

Funding Scheme: MSCA-IF-EF-ST - Standard EF

Grant agreement ID: 101025483

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.