Immediate early gene expression dynamics in vivo segregates neuronal ensemble of multiple memories.

Abstract

Immediate early genes (IEGs) are widely used as a marker for neuronal plasticity. Here, we model the dynamics of IEG expression as a consecutive, irreversible first order reaction with a limiting substrate. We show that such a model, together with two-photon in vivo imaging of IEG expression, can be used to identify distinct neuronal subsets representing multiple memories. We image retrosplenial cortex (RSc) of cFOS-GFP transgenic mice to follow the dynamics of cellular changes resulting from both seizure and contextual fear conditioning behaviour. The analytical expression allowed us to segregate the neurons based on their temporal response to one specific behavioural event, thereby improving the sensitivity of detecting plasticity related neurons. This enables us to establish representation of context in RSc at the cellular scale following memory acquisition. Thus, we obtain a general method which distinguishes neurons that took part in multiple temporally separated events, by measuring fluorescence from individual neurons in live mice. SummaryIdentifying neuronal ensemble associated with different memories is vital in modern neuroscience. Meenakshi et al model and use the temporal expression dynamics of IEGs rather than thresholded intensities of the probes to identify the neurons encoding different memory in vivo. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/423270v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1d6c197org.highwire.dtl.DTLVardef@3fca7aorg.highwire.dtl.DTLVardef@64615org.highwire.dtl.DTLVardef@1e30dbc_HPS_FORMAT_FIGEXP M_FIG C_FIG