Spiegel, I. | bioRxiv Science

bioRxiv2024

Daily light-induced transcription in visual cortex neurons drives downward Firing Rate Homeostasis and stabilizes sensory processing

Balancing plasticity and stability in neural circuits is essential for an animals ability to learn from its environment while preserving the proper processing and perception of sensory information. However, unlike the mechanisms that drive plasticity in neural circuits, the activity-induced molecular mechanisms that convey functional stability remain poorly understood. Focusing on the visual cortex of adult mice and combining transcriptomics, electrophysiology and 2-photon imaging, we find that the daily appearance of light induces in excitatory neurons a large gene program along with rapid and transient shifts in the ratio of excitation and inhibition (E/I-ratio) and ongoing neural activity. Furthermore, we find that the light-induced transcription factor NPAS4 drives these daily normalizations of E/I-ratio and neural activity rates and that it stabilizes the neurons response properties. These findings indicate that daily sensory-induced transcription normalizes E/I-ratio and drives downward Firing Rate Homeostasis to maintain proper sensory processing and perception.

neuroscience↗

bioRxiv2024

2P-NucTag: on-demand phototagging for molecular analysis of functionally identified cortical neurons

Neural circuits are characterized by genetically and functionally diverse cell types. A mechanistic understanding of circuit function is predicated on linking the genetic and physiological properties of individual neurons. However, it remains highly challenging to map the molecular properties onto functionally heterogeneous neuronal subtypes in mammalian cortical circuits in vivo. Here, we introduce a high-throughput two-photon nuclear phototagging (2P-NucTag) approach for on-demand and indelible labeling of single neurons via a photoactivatable red fluorescent protein following in vivo functional characterization in behaving mice. Using this novel function-forward pipeline to selectively label and transcriptionally profile previously inaccessible place and silent cells in the hippocampus of behaving mice, we identify unexpected differences in gene expression between these hippocampal pyramidal neurons with distinct spatial coding properties. Thus, 2P-NucTag opens a new way to uncover the molecular principles that govern the functional organization of neural circuits. One-Sentence Summary2P-NucTag - A novel high-throughput on-demand phototagging approach to identify selective gene expression of functionally distinct neurons in vivo in behaving animals.

neuroscience↗