Activity labeling in vivo using CaMPARI2 reveals intrinsic and synaptic differences between neurons with high and low firing rate set points

Abstract

Neocortical pyramidal neurons regulate firing around a stable mean firing rate (FR) that can differ by orders of magnitude between neurons, but the factors that determine where individual neurons sit within this broad FR distribution are not understood. To access low- and high-FR neurons for ex vivo analysis, we used Ca2+- and UV-dependent photoconversion of CaMPARI2 in vivo to permanently label neurons according to mean FR. CaMPARI2 photoconversion was correlated with immediate early gene expression and higher FRs ex vivo and tracked the drop and rebound in ensemble mean FR induced by prolonged monocular deprivation. High-activity L4 pyramidal neurons had greater intrinsic excitability and recurrent excitatory synaptic strength, while E/I ratio, local output strength, and local connection probability were not different. Thus, in L4 pyramidal neurons (considered a single transcriptional cell type), a broad mean FR distribution is achieved through graded differences in both intrinsic and synaptic properties. Which neuronal properties endow neurons with disparate firing set points is unknown. Trojanowski et al. use CaMPARI2 to permanently label L4 pyramidal neurons based on in vivo mean FR and find that mean FR is correlated with intrinsic excitability and local input strength but not output strength or E/I ratio.