ArticleMolecular brain2026
Npas4 regulates synaptic development in the patch/striosome compartment and early affective vocalization in neonatal mice.
Article in Molecular brain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Early vocal communication, such as isolation-induced ultrasonic vocalization (USV) in neonatal rodents, is critical for infant survival and represents a primary readout of early affective states. The patch/striosome compartment in the striatum has been proposed to serve as a limbic-motor interface integrating emotion and motivation. Developmentally, this compartment undergoes early maturation, during which activity-dependent transcription factors might enable the functional assembly of limbic-striosomal circuits to regulate infant vocal-motor behavior. Npas4, an activity-dependent early-response transcription factor, controls the developmental balance of excitatory and inhibitory synaptic activity. Here, we investigated how patch/ striosome compartment-expressing Npas4 shapes early synaptic development and neonatal vocalization. We found that Npas4 transcripts were transiently enriched in patch/striosomes at postnatal days (P) 4 and P8, before adopting a homogenous striatal distribution by P14. To investigate its biological function, we generated a patch/striosome-specific Npas4 conditional knockout. Anatomically, Npas4 deletion disrupted patch/striosomal synaptic balance, evidenced by a significant reduction in excitatory (Vglut1) and an increase in inhibitory (Vgat) presynaptic terminals. Behaviorally, acoustic and Markov-chain syntactical analyses of isolation-induced USVs revealed a hyper-vocal phenotype at P8, characterized by a significant increase in total USV call numbers and augmented temporal clustering of vocal bouts and sequences. Furthermore, acoustic analysis demonstrated a shift toward more complex syllable types. While the structure of global transition networks was preserved, Npas4 knockout mice exhibited an elevated sequence entropy rate, indicating greater moment-to-moment structural variability. Our study suggests that Npas4 shapes the development of limbic-striosomal circuits to provide top-down gating of early affective vocalization in neonates.
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