Cortical functional subnetworks in the fosGFP+ mouse

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The central question of this proposal is: do L2 pyramidal neurons form functional connected subnetworks of excitatory neurons with distinct sensory processing properties in the fosGFP mouse? Neurons in the fosGFP mouse express GFP under the regulation of the activity dependent, immediate early gene c-fos. About 10% of L2 and L6 pyramidal neurons are more strongly labelled with GFP. Over the previous funding period we have developed in vivo double and triple two-photon targeted recordings to record routinely from nearby (<100 μm) L2 pyramidal neurons in the anaesthetised fosGFP transgenic mouse. In our report, we show that in vivo fosGFP+ expressing L2 pyramidal neurons have increased spontaneous firing rates with larger amplitude synaptic input during upstates and show distinct sensory responses as compared to fosGFP- neurons. The sensory response to whisker stimulation in GFP expressing neurons is earlier and has larger amplitude than the response in GFP- pyramidal neurons. Brain slice connectivity data from the same mouse line suggests that fosGFP+ neurons are more connected to each other than to fosGFP- neurons. Together this raises the possibility that the fosGFP+ neurons are a functionally distinct subnetwork of more connected pyramidal neurons. Here we propose to use this mouse line to perform two central experiments: (i) use in vivo 2-photon targeted whole-cell recordings to correlate synaptic connectivity with sensory responses and spontaneous activity in connected / unconnected fosGFP+/ fosGFP- neurons in L2 of anaesthetised mice; (ii) perform in vivo juxtacellular recordings and stainings of L2 and L6 fosGFP+ neurons in anaesthetised and awake mice, in collaboration with the group of Prof. Dirk Feldmeyer and Prof Jochen Staiger, to investigate whether fosGFP+ neurons have distinct anatomical features and similar functional properties in different cortical layers. Taken together, the anatomical and physiological data will help us examine whether the fosGFP+ neurons form functional subnetworks in vivo.