Functional correlates of immediate early gene expression in mouse visual cortex

Abstract

During visual development, response properties of layer 2/3 neurons in visual cortex are shaped by experience. Both visual and visuomotor experience are necessary to coordinate the integration of bottom-up visual input and top-down motor-related input. Whether visual and visuomotor experience engage different plasticity mechanisms, possibly associated with the two separate input pathways, is still unclear. To begin addressing this, we measured the expression level of three different immediate early genes (IEG) (c-fos, egr1 or Arc) and neuronal activity in layer 2/3 neurons of visual cortex before and after a mouse's first visual exposure in life, and subsequent visuomotor learning. We found that expression levels of all three IEGs correlated positively with neuronal activity, but that first visual and first visuomotor exposure resulted in differential changes in IEG expression patterns. In addition, IEG expression levels differed depending on whether neurons exhibited primarily visually driven or motor-related activity. Neurons with strong motor-related activity preferentially expressed EGR1, while neurons that developed strong visually driven activity preferentially expressed Arc. Our findings are consistent with the interpretation that bottom-up visual input and top-down motor-related input are associated with different IEG expression patterns and hence possibly also with different plasticity pathways.

Functional connectivity favors aberrant visual network c-Fos expression accompanied by cortical synapse loss in a mouse model of Alzheimer’s disease

“…Consistently, we also observed an increase in the expression of the immediate early gene c-Fos in the primary visual cortex of an amyloid mouse model (Niraula et al, 2023). c-Fos is rapidly and transiently expressed following membrane depolarization and calcium influx in some neurons (Barth, Gerkin and Dean, 2004;Kawashima, Okuno and Bito, 2014;Mahringer et al, 2022;Morgan et al, 1987;Yap and Greenberg, 2018;Zangenehpour and Chaudhuri, 2002). Its low baseline expression, widespread expression profile, and close associations with learning and memory recall have made c-Fos + cell labeling an attractive tool for mapping and manipulating experience and memory associated neuronal ensembles (Barth, Gerkin and Dean, 2004;Guenthner et al, 2013;Liu et al, 2012;Reijmers et al, 2007).…”

Molecular tools to capture active neural circuits

“…While many studies have reported using these tools in the hippocampus, it has been noted that the labeling sensitivity of pyramidal neurons in the CA1 and CA3 regions is lower than that of the granule cells in the dentate gyrus when using TetTag or TRAP2 mice ( Deng et al, 2013 ; Leake et al, 2021 ). Additionally, neurons belonging to functionally distinct circuits tend to express different IEGs ( Mahringer et al, 2022 ).…”

Neuronal FOS reports synchronized activity of presynaptic neurons

“…In vivo calcium imaging studies also found surprisingly weak correlations between the frequency or amplitude of calcium transients and FOS expression in individual neurons during learning (14)(15)(16). As its complex transcriptional regulation already suggests, FOS seems to be more than a simple reporter of intracellular calcium or spike frequency.…”

“…In cultured neurons, stimuli delivered in repetitive short bursts drive FOS more efficiently than long duration trains of single action potentials, but FOS induction was not correlated with intracellular calcium levels ( 11–13 ). In vivo calcium imaging studies also found surprisingly weak correlations between the frequency or amplitude of calcium transients and FOS expression in individual neurons during learning ( 14–16 ). As its complex transcriptional regulation already suggests, FOS seems to be more than a simple reporter of intracellular calcium or spike frequency.…”