Multiscale regulation of experience-dependent plasticity by a Pannexin1 homolog in a developing vertebrate brain

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Abstract Experience-dependent plasticity enables the developing brain to adapt to repeated sensory input while maintaining stability. However, how such plasticity is coordinated across behavior, transcription, and network dynamics remains unclear. Here, using larval zebrafish, we identify the pannexin channel homolog, Panx1a as a regulator of multiscale adaptations during visual habituation. Panx1a loss selectively impairs long-term habituation without affecting baseline sensorimotor responses. This behavioral deficit is accompanied by disrupted activity-dependent transcription across distributed brain regions and altered excitation-inhibition balance. At the network level, Panx1a deficiency attenuates experience-dependent modulation of gamma activity, cross-frequency coupling, and inter-regional coherence. We further show that sharp wave-ripple-like events are present in vivo at an early developmental stage and exhibit selective refinement of their sharp-wave component following experience, while ripple features remain largely unchanged. This refinement is reduced in panx1a mutants, indicating a role for Panx1a in shaping network dynamics rather than event generation. Together, these findings identify Panx1a as a mediator linking extracellular signaling to coordinated behavioral, molecular, and circuit-level plasticity during early brain development.

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