Biology subjects

Nip, K.

Publications and source records attributed to Nip, K..

4 recordsLinked to original sources

bioRxiv2024

Impacts of Perinatal Nicotine Exposure on nAChR Expression and Glutamatergic Synaptic Transmission in the Mouse Auditory Brainstem

Exposure to nicotine in utero, often due to maternal smoking, significantly elevates the risk of auditory processing deficits in offspring. This study investigated the effects of chronic nicotine exposure during a critical developmental period on the functional expression of nicotinic acetylcholine receptors (nAChRs), glutamatergic synaptic transmission, and auditory processing in the mouse auditory brainstem. We evaluated the functionality of nAChRs at a central synapse and explored the impact of perinatal nicotine exposure (PNE) on synaptic currents and auditory brainstem responses (ABR) in mice. Our findings revealed developmentally regulated changes in nAChR expression in the medial nucleus of the trapezoid body (MNTB) neurons and presynaptic Calyx of Held terminals. PNE was associated with enhanced acetylcholine-evoked postsynaptic currents and compromised glutamatergic neurotransmission, highlighting the critical role of nAChR activity in the early stages of auditory synaptic development. Additionally, PNE resulted in elevated ABR thresholds and diminished peak amplitudes, suggesting significant impairment in central auditory processing without cochlear dysfunction. This study provides novel insights into the synaptic disturbances that contribute to auditory deficits resulting from chronic prenatal nicotine exposure, underlining potential targets for therapeutic intervention.

neuroscience↗

bioRxiv2024

Scn2a deletion disrupts oligodendroglia function: Implication for myelination, neural circuitry, and auditory hypersensitivity in ASD

Autism spectrum disorder (ASD) is characterized by a complex etiology, with genetic determinants significantly influencing its manifestation. Among these, the Scn2a gene emerges as a pivotal player, crucially involved in both glial and neuronal functionality. This study elucidates the underexplored roles of Scn2a in oligodendrocytes, and its subsequent impact on myelination and auditory neural processes. The results reveal a nuanced interplay between oligodendrocytes and axons, where Scn2a deletion causes alterations in the intricate process of myelination. This disruption, in turn, instigates changes in axonal properties and neuronal activities at the single cell level. Furthermore, oligodendrocyte-specific Scn2a deletion compromises the integrity of neural circuitry within auditory pathways, leading to auditory hypersensitivity--a common sensory abnormality observed in ASD. Through transcriptional profiling, we identified alterations in the expression of myelin-associated genes, highlighting the cellular consequences engendered by Scn2a deletion. In summary, the findings provide unprecedented insights into the pathway from Scn2a deletion in oligodendrocytes to sensory abnormalities in ASD, underscoring the integral role of Scn2a-mediated myelination in auditory responses. This research thereby provides novel insights into the intricate tapestry of genetic and cellular interactions inherent in ASD.

neuroscience↗

bioRxiv2023

The autism-associated loss of δ-catenin functions disrupts social behaviors

{delta}-catenin is expressed in excitatory synapses and functions as an anchor for the glutamatergic AMPA receptor (AMPAR) GluA2 subunit in the postsynaptic density. The glycine 34 to serine (G34S) mutation in the{delta} -catenin gene is found in autism spectrum disorder (ASD) patients and induces loss of {delta}-catenin functions at excitatory synapses, which is presumed to underlie ASD pathogenesis in humans. However, how the G34S mutation causes loss of {delta}-catenin functions to induce ASD remains unclear. Here, using neuroblastoma cells, we discover that the G34S mutation generates an additional phosphorylation site for glycogen synthase kinase 3{beta} (GSK3{beta}). This promotes {delta}-catenin degradation and causes the reduction of {delta}-catenin levels, which likely contributes to the loss of {delta}-catenin functions. Synaptic {delta}-catenin and GluA2 levels in the cortex are significantly decreased in mice harboring the {delta}-catenin G34S mutation. The G34S mutation increases glutamatergic activity in cortical excitatory neurons while it is decreased in inhibitory interneurons, indicating changes in cellular excitation and inhibition. {delta}-catenin G34S mutant mice also exhibit social dysfunction, a common feature of ASD. Most importantly, inhibition of GSK3{beta} activity reverses the G34S-induced loss of {delta}-catenin function effects in cells and mice. Finally, using {delta}-catenin knockout mice, we confirm that {delta}-catenin is required for GSK3{beta} inhibition-induced restoration of normal social behaviors in {delta}-catenin G34S mutant animals. Taken together, we reveal that the loss of {delta}-catenin functions arising from the ASD-associated G34S mutation induces social dysfunction via alterations in glutamatergic activity and that GSK3{beta} inhibition can reverse {delta}-catenin G34S-induced synaptic and behavioral deficits. Significance Statement{delta}-catenin is important for the localization and function of glutamatergic AMPA receptors at synapses in many brain regions. The glycine 34 to serine (G34S) mutation in the{delta} -catenin gene is found in autism patients and results in the loss of {delta}-catenin functions. {delta}-catenin expression is also closely linked to other autism-risk genes involved in synaptic structure and function, further implying that it is important for the autism pathophysiology. Importantly, social dysfunction is a key characteristic of autism. Nonetheless, the links between {delta}-catenin functions and social behaviors are largely unknown. The significance of the current research is thus predicated on filling this gap by discovering the molecular, cellular, and synaptic underpinnings of the role of {delta}-catenin in social behaviors.

neuroscience↗

bioRxiv2020

Structural refinement of the auditory brainstem neurons in baboons during perinatal development

Children born prematurely suffer from learning disabilities and exhibit reading, speech, and cognitive difficulties, which are associated with an auditory processing disorder. However, it is unknown whether gestational age at delivery and the unnatural auditory environment in neonatal intensive care units (NICU) collectively affect proper auditory development and neuronal circuitry in premature newborns. We morphologically characterized fetal development of the medial superior olivary nucleus (MSO), an area important for binaural hearing and sound localization, in the auditory brainstem of baboon neonates at different gestational ages. Axonal and synaptic structures and the tonotopic differentiation of ion channels in the MSO underwent profound refinements after hearing onset in the uterus. In preterm baboon neonates, these developmental refinements of the MSO were significantly altered by limited maternal sound inputs from the isolated and unnatural environment in the NICU. Thus, the maternal environment, including auditory stimuli in uterus, is essential for auditory nervous system development during the last trimester of pregnancy and critically affects the anatomic and functional formation of synapses and neural circuitry in the preterm newborn brain.

developmental biology↗