Description
The neocortex is essential for higher-order brain functions such as cognition, perception, language, and motor commands, facilitated by networks of brain cells that process sensory inputs and motor actions. To understand intercellular communication in the neocortex, we investigated the role of extracellular signal-regulated kinase (ERK), which regulates various cellular processes including differentiation, proliferation, and migration. While ERK activity in hippocampal neurons is well-studied for its role in memory formation, the spatiotemporal ERK activity dynamics in awake mice brain remains unclear. In this study, we used Förster resonance energy transfer (FRET)-based probes and two-photon microscopy to examine ERK activity. We employed hyBRET-ERKnls transgenic mice, which express the FRET-based ERK biosensor hyBRET-ERK-NLS in the nuclei, for in vivo imaging of layer 2/3 neocortical cells through a cranial window. Visual cortical neurons exhibited ERK activation in response to visual stimuli, with approximately 10% of cells showing NMDA receptor-dependent increase in ERK activity. Beyond stimulus-induced activation, we also discovered spontaneous, stochastic ERK activation patterns categorized as single, multi-pulsatile, and sustained activations. These activation patterns were consistent across various subcortical regions, including the visual and somatosensory cortices. Furthermore, synchronized ERK activation among neurons was observed, suggesting a coordinated ERK activation mechanism within neuronal networks that may contribute to sensory processing and motor control. These findings reveal highly dynamic ERK activation in neocortical cells and provide new insights into the functional role of ERK in the awake brain. Keywords: ERK dynamics, two-photon imaging, NMDA receptor dependency, neuronal synchronization, awake mouse neocortex
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