Biology subjects

Tamaki, A.

Publications and source records attributed to Tamaki, A..

3 recordsLinked to original sources

bioRxiv2026

The mouse midbrain periaqueductal gray is organized into target-specific output populations

How brains select between behaviours and coordinate their execution is a central question in neuroscience. The vertebrate periaqueductal gray (PAG) controls a remarkable range of instinctive behaviours, from escape and freezing to hunting, vocalization, and micturition. Its columnar organization, the classical framework for mapping these functions, cannot explain how one region controls so many, often mutually exclusive, behaviours. To determine how PAG output is organized, we generated a whole-brain, column- and cell-type-specific synaptic projection atlas of the mouse PAG, showing distinct dorsal and ventral outputs and dense within-PAG connectivity. Retrograde tracing from four motor-related target regions identified segregated PAG populations, biased towards, but not confined to, individual columns. Channelrhodopsin-2-assisted circuit mapping showed that one such population, projecting to the cuneiform nucleus, provides substantial local collaterals, positioned to shape ongoing PAG activity. These findings uncover a modular output architecture that extends the columnar framework, offering a circuit logic for how one brain region produces diverse behaviours.

neuroscience↗

bioRxiv2026

DARPP-32 in motor cortex regulates structural and synaptic plasticity in corticothalamic neurons and enables motor learning.

The dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a key mediator of monoaminergic signaling, is expressed in the cortex; however, its cellular distribution and role in cortically dependent behaviors remain elusive. Here, we determined the functional integration of DARPP-32 in motor cortex circuitry using molecular profiling, circuit tracing, patch-clamp electrophysiology, virus-assisted gene targeting and motor behavior analyses. Unlike the significant overlap between DARPP-32 and dopamine receptors in striatal GABAergic medium spiny projection neurons, we found that the majority of DARPP-32-positive cortical neurons express the corticothalamic marker FoxP2 but not dopamine D1 or D2 receptors. Notably, in cortical slices, adenylyl cyclase activation induced a more robust increase in DARPP-32 phosphorylation at threonine 34, a protein kinase A target site, compared to dopamine D1 receptor stimulation. Conditional ablation of DARPP-32 in the motor cortex did not affect basal or psychostimulant-induced motor activity but reduced motor aptitude and compromised overnight retention of motor skill. Concomitantly, the absence of DARPP-32 reduced dendritic spines density and prevented the induction of glutamatergic long-term potentiation in layer 6 motor cortical neurons. Altogether, our study demonstrates a critical role for DARPP-32 in cortical synaptic plasticity, emphasizing its importance in corticothalamic regulation of motor skill learning.

neuroscience↗

bioRxiv2025

Postnatal reduction of eIF4E overexpression in D1-SPNs ameliorates KCNQ dysfunction, hyperexcitability and ASD-like behaviours.

An imbalance between the direct and indirect pathways of the striatum has been implicated in the pathophysiology of ASD, which corresponds with an increase in repetitive behaviours and hyperactivity. The ASD risk gene EIF4E promotes translation, and its overexpression in mice increases repetitive behaviours and hyperactivity. We used the eIF4E-transgenic mouse model of ASD to study cell-type specific disruptions in the direct and indirect pathways using fibre photometry, electrophysiology, conditional gene silencing, and behavioural analysis. We found that direct pathway SPNs activity increased during exploratory behaviour and identified D1-SPN hyperexcitability and reduced KCNQ channel function in striatal slices. Reduction of eIF4E specifically in the D1-SPNs of adult mice normalised KCNQ function, D1-SPN hyperexcitability and ameliorated repetitive and hyperactive behaviours. Our results highlight the critical role of eIF4E in ASD-associated motor behaviours, elucidate cell-specific mechanisms driving hyperactivity and provide new insight into potential therapeutic targets for ASD and other neurodevelopmental disorders. Overall, this study underscores the translational potential of modulating protein synthesis pathways to address core motor symptoms in ASD.

neuroscience↗