Wollet Mackenna, Hernandez Abram, Nip Kaila, Ginsburg Brett, Pugh Jason R, Kim Jun Hee
Department of Cellular and Integrative Physiology, UT Health San Antonio, San Antonio, Texas, USA.
Department of Psychiatry and Behavioral Science, UT Health San Antonio, San Antonio, Texas, USA.
J Physiol. 2025 May;603(9):2857-2876. doi: 10.1113/JP286971. Epub 2025 May 5.
In utero nicotine exposure from maternal smoking is linked to increased risk of auditory processing deficits. This study investigated the impact of developmental nicotine exposure during the critical period on nicotinic acetylcholine receptor (nAChR) functional expression, glutamatergic synaptic transmission and auditory processing in the mouse auditory brainstem. We assessed nAChR function at a central synapse and the consequences of perinatal nicotine exposure (PNE) on synaptic currents and auditory brainstem responses (ABRs) in mice. Our results indicate developmentally regulated changes in nAChR expression in medial nucleus of the trapezoid body (MNTB) neurons and presynaptic calyx of Held terminals. PNE led to increased ACh-evoked postsynaptic currents and impaired glutamatergic neurotransmission, underscoring the importance of nAChR activity in early auditory synaptic development. PNE also increased ABR thresholds and reduced ABR peak amplitudes, indicating impaired central auditory processing without cochlear dysfunction. Our study provides new insights into the synaptic disruptions underlying auditory deficits from prenatal nicotine exposure. KEY POINTS: In utero nicotine exposure leads to increased risk of sensory processing deficits and elevated expression of nicotinic acetylcholine receptors (nAChRs). nAChRs are essential for auditory processing and are present in the auditory brainstem. Within the medial nucleus of the trapezoid body in the auditory brainstem, the patterning of nicotinic receptor expression during development and how nicotine exposure might affect this are unknown. Nicotinic receptors are expressed postsynaptically before hearing onset and switch to presynaptic expression after hearing onset. Perinatal nicotine exposure disrupts physiological nicotinic receptor patterning and impairs synaptic transmission at the calyx of Held.
母亲吸烟导致的子宫内尼古丁暴露与听觉处理缺陷风险增加有关。本研究调查了关键期发育性尼古丁暴露对小鼠听觉脑干中烟碱型乙酰胆碱受体（nAChR）功能表达、谷氨酸能突触传递和听觉处理的影响。我们评估了中枢突触处的nAChR功能以及围产期尼古丁暴露（PNE）对小鼠突触电流和听觉脑干反应（ABR）的影响。我们的结果表明，梯形体内侧核（MNTB）神经元和Held终末突触前花萼中nAChR表达存在发育调节变化。PNE导致乙酰胆碱诱发的突触后电流增加和谷氨酸能神经传递受损，突出了nAChR活性在早期听觉突触发育中的重要性。PNE还增加了ABR阈值并降低了ABR峰值幅度，表明中枢听觉处理受损但无耳蜗功能障碍。我们的研究为产前尼古丁暴露导致听觉缺陷的潜在突触破坏提供了新的见解。要点：子宫内尼古丁暴露导致感觉处理缺陷风险增加和烟碱型乙酰胆碱受体（nAChRs）表达升高。nAChRs对听觉处理至关重要，存在于听觉脑干中。在听觉脑干的梯形体内侧核内，发育过程中烟碱型受体表达的模式以及尼古丁暴露如何影响这种模式尚不清楚。烟碱型受体在听力开始前在突触后表达，听力开始后转换为突触前表达。围产期尼古丁暴露会破坏生理性烟碱型受体模式，并损害Held花萼处的突触传递。
