Biology subjects

Yokoi, Y.

Publications and source records attributed to Yokoi, Y..

3 recordsLinked to original sources

bioRxiv2026

Haploidy-linked disruption of tissue organization in zebrafish larval eyes

In vertebrate species, somatic haploidy generally causes embryonic or larval lethality with drastic morphological defects. However, the detrimental effects of haploidy at the cellular or tissue level remain largely unknown. In this study, we described cellular and tissue defects associated with haploidy in zebrafish larval eyes as a tissue model system. The haploid larval retina showed overall disorganized tissue layer structures. Photoreceptor cells, which usually align in the outermost tissue layer, were reduced in number and severely displaced, with drastic retardation of their connecting cilia and outer segments specifically in haploids. Ganglion cells in the inner retinal layer were also reduced in abundance and abnormally organized in haploids. These multifaceted cellular and tissue defects indicate that haploid eyes suffer severe visual functional defects, in addition to well-recognized size reductions. Our findings provide insight into diverse cellular principles that may limit the developmental capability of vertebrates in the haploid state.

developmental biology↗

bioRxiv2026

Reduced cortico-accumbal excitatory input due to Nav1.2 haploinsufficiency impairs sociability independently of dopamine

Mutations in SCN2A, which encodes the voltage-gated sodium channel Nav1.2, are associated with a wide spectrum of neurodevelopmental and neuropsychiatric disorders, including epilepsy, autism spectrum disorder (ASD), and schizophrenia. Although dysfunction of SCN2A-dependent neural circuits has been implicated in these disorders, the circuit mechanisms underlying social behavioral abnormalities remain poorly understood. Here, we investigated the neural circuit basis of social behavioral deficits associated with Scn2a dysfunction, focusing on the nucleus accumbens (NAc), a key hub in cortico-limbic circuits that regulates emotional and motivational behaviors. Using conditional genetic and chemogenetic approaches in mice, we examined the roles of dorsal telencephalic excitatory neurons, including those in the cerebral cortex, hippocampus, and amygdala, as well as parvalbumin-positive fast-spiking interneurons (PV FSIs) in the NAc. Mice with Scn2a haploinsufficiency in dorsal telencephalic excitatory neurons (Scn2afl/+/Emx1-Cre) exhibited reduced sociability in the three-chamber social interaction test. Similarly, chemogenetic inhibition of NAc PV FSIs decreased sociability without affecting locomotor activity or anxiety-like behavior. Scn2afl/+/Emx1-Cre mice also showed a trend toward reduced prepulse inhibition of the acoustic startle response. Notably, dopamine release into the NAc in the Scn2afl/+/Emx1-Cre and systemic Scn2a heterozygous knockout (Scn2a+/-) mice was largely comparable to that in control mice. Together, these findings indicate that reduced activity of dorsal telencephalic excitatory neurons or NAc PV FSIs is sufficient to impair sociability independently of mesolimbic dopamine hypofunction. Our results highlight a potential role of cortico-accumbal circuits in social behavioral deficits associated with SCN2A dysfunction.

neuroscience↗

bioRxiv2025

Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility

Memory expression fluctuates even in response to identical cues, suggesting that ongoing brain states bias memory accessibility. However, the cellular and circuit principles governing these state-dependent fluctuations remain unclear. Here, we show that spontaneous pre-cue activity of histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) modulates the expression of reward-associative memory in mice. TMN histaminergic activity exhibited infraslow dynamics (0.05-0.1 Hz) that closely tracked an integrated brain-body state. Closed-loop cue delivery during high histaminergic states enhanced memory expression. Brief optogenetic activation or inhibition of these neurons before the cue bidirectionally modulated memory expression, and direct activation of histaminergic terminals in the basolateral amygdala (BLA) was sufficient to enhance memory expression. Furthermore, histaminergic inhibition before the cue impaired the cue-evoked BLA population response. Thus, ongoing histaminergic activity exerts an infraslow, state-setting influence that primes BLA circuits for robust cue responses, and in turn, modulates moment-to-moment memory accessibility.

neuroscience↗