Biology subjects

Matsuzaki, H.

Publications and source records attributed to Matsuzaki, H..

4 recordsLinked to original sources

bioRxiv2026

Auricular vagus nerve stimulation facilitates contextual fear extinction via insular-mPFC pathway without affecting reconsolidation

Cervical vagus nerve stimulation (VNS) suppresses conditioned fear in rodents and may serve as an adjunct to exposure-based therapy for anxiety disorders. Non-invasive auricular VNS reduces conditioned fear also in humans, although the underlying mechanisms remain unclear. Using a contextual fear conditioning paradigm, in which brief re-exposure induces reconsolidation and prolonged re-exposure promotes extinction learning in mice, we examined auricular VNS-induced attenuation of fear. Auricular VNS during prolonged but not during brief re-exposures reduced freezing, indicating selective facilitation of extinction learning. Stimulation during the latter half of prolonged re-exposure, while extinction learning was progressing, reduced fear responses. As a neural circuit mechanism, we focused on projections from the posterior insular cortex (pIC), which receives interoceptive signals, including vagal input, to the medial prefrontal cortex (mPFC), which regulates fear. Auricular VNS increased c-Fos expression in pIC neurons projecting to the mPFC subdivisions: infralimbic and dorsal peduncular cortex (IL/DP). Optogenetic activation of the pIC-IL/DP pathway mimicked the extinction-facilitating effects of auricular VNS, whereas inhibition blocked them. These results demonstrate that auricular VNS promotes extinction learning of contextual fear memory by activating the pIC-IL/DP circuit, providing insight into how vagal afferent stimulation engages insular-prefrontal networks to modulate fear.

neuroscience↗

bioRxiv2025

N-Ethylmaleimide-Sensitive Factor Deletion in Dopamine D2 Receptor Cells and Associated Neuronal and Behavioural Changes in Mice

N-ethylmaleimide-sensitive factor (NSF) plays a crucial role in neurotransmitter release and membrane molecule trafficking by regulating membrane fusion. Dysfunction of NSF has been linked to neuropsychiatric disorders. Although the interaction of NSF with dopamine receptor 2 (D2R) and the resulting excitotoxicity from its reduction in vitro have been demonstrated, the role of NSF in D2R-expressing cells in vivo remains unclear. This study investigated the effects of NSF loss on the survival of D2R-expressing cells and on mouse behaviour. We generated D2R-specific NSF conditional knockout (Nsff/f;D2R-Cre) mice. Targeted deletion of NSF in D2R-expressing cells led to a significant decrease in D2R-expressing neurons, accompanied by increased apoptosis during postnatal development, reduced striatal volume, and substantially lowered dopamine levels in the striatum. Further evidence of dopaminergic dysfunction was shown by reduced dopamine transporter expression in the striatum and tyrosine hydroxylase expression in the striatum and substantia nigra. The Nsff/f;D2R-Cre mice exhibited attention deficit hyperactivity disorder (ADHD)-like behaviours, including hyperactivity and impulsivity. Notably, combined administration of methylphenidate and a D2R agonist effectively alleviated hyperactivity and impulsivity, indicating a potential synergistic approach for ADHD treatment. These findings highlight the critical role of NSF in the survival of D2R-expressing neurons and suggest that disruption of the NSF-D2R interaction may contribute to ADHD-like phenotypes. This study underscores the translational relevance of the Nsff/f;D2R-Cre model for ADHD and suggests that targeting D2R dysfunction, particularly in treatment-resistant cases, may represent a promising therapeutic strategy for ADHD.

neuroscience↗

bioRxiv2020

Zbtb16 regulates social cognitive behaviors and neocortical development.

Recent genetic studies have underscored the pleiotropic effects of single genes to multiple cognitive disorders. Mutations of ZBTB16 are associated with autism spectrum disorder (ASD) and schizophrenia (SCZ), but how the function of ZBTB16 is related to ASD or SCZ remains unknown. Here we show the deletion of Zbtb16 in mice leads to both ASD- and SCZ-like behaviors such as social impairment, repetitive behaviors, risk-taking behaviors, and cognitive impairment. To elucidate the mechanism underlying the behavioral phenotypes, we carried out histological studies and observed impairments in thinning of neocortical layer 6 (L6) and a reduction of TBR1+ neurons in the prefrontal cortex (PFC) of Zbtb16 KO mice. Furthermore, we found increased dendritic spines and microglia as well as developmental defects in oligodendrocytes and neocortical myelination in the PFC of Zbtb16 KO mice. Using a genomics approach, we identified the Zbtb16-transcriptome that includes genes involved in both ASD and SCZ pathophysiology and neocortical maturation such as neurogenesis and myelination. Co-expression networks further identified Zbtb16-correlated modules that are unique to ASD or SCZ respectively. Our study provides insight into the differential role of ZBTB16 in ASD and SCZ.

neuroscience↗

bioRxiv2018

No evidence for transvection in vivo by a superenhancer:promoter pair integrated into identical open chromatin at the Rosa26 locus

Long-range associations between enhancers and their target gene promoters have been shown to play critical roles in executing genome function. Recent variations of chromosome capture technology have revealed a conprehensive view of intra- and inter-chromosomal contacts between specific genomic sites. The locus control region of the {beta}-globin genes ({beta}-LCR) is a super-enhancer that is capable of activating all of the {beta}-like globin genes within the locus in cis through physical interaction by forming DNA loops. CTCF helps to mediate loop formation between LCR-HS5 and 3HS1 in the human {beta}-globin locus, in this way thought to contribute to the formation of a \"chromatin hub\". The {beta}-globin locus is also in close physical proximity to other erythrocyte-specific genes located long distances away on the same chromosome. In this case, erythrocyte-specific genes gather together at a shared \"transcription factory\" for co-transcription. Theoretically, enhancers could also activate target gene promoters on different chromosomes in trans, a phenomenon originally described as transvection in Drosophilla. Although close physical proximity has been reported for the {beta}-LCR and the {beta}-like globin genes when integrated at the mouse homologous loci in trans, their structural and functional interactions were found to be rare, possibly because a lack of suitable regulatory elements that might facilitate trans interactions. Therefore, we re-evaluated presumptive transvection-like enhancer-promoter communication by introducing CTCF binding sites and erythrocyte-specific transcription units into both LCR-enhancer and {beta}-promoter alleles, each inserted into the mouse ROSA26 locus on separate chromosomes. Following cross-mating of mice to place the two mutant loci at the identical chromosomal position and into active chromation in trans, their transcriptional output was evaluated. The results demonstrate that there was no significant functional association between the LCR and the {beta}-globin gene in trans even in this idealized experimental context.

genomics↗