Tufo Candida, Cheah Menghon, Lipovsek Marcela, Byrne Darren J, Kothandapani Krishna, Browne Lorcan P, Grubb Matthew S
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
Ear Institute, University College London, London, UK.
Eur J Neurosci. 2025 Jul;62(1):e70188. doi: 10.1111/ejn.70188.
Continued integration of new neurons persists in only a few areas of the adult mouse brain. In the olfactory bulb (OB), immature adult-born neurons respond differently to olfactory stimuli compared to their more mature counterparts and have heightened levels of activity-dependent plasticity. These distinct functional features are thought to bestow unique properties onto existing circuitry. OB interneurons, including those generated through adult neurogenesis, consist of a set of highly distinct subtypes. However, we do not currently know the different cell-type-specific mechanisms underlying their functional development and plastic potential. Here, we specifically characterised electrophysiological maturation and experience-dependent plasticity in a single, defined subtype of adult-born OB neuron: dopaminergic cells. We selectively live-labelled both adult-born and 'resident' dopaminergic cells, and targeted them for whole-cell patch-clamp recordings in acute mouse OB slices. Surprisingly, we found that from the time-at ~1 month of cell age-that live adult-born dopaminergic neurons could first be reliably identified, they already possessed almost fully mature intrinsic firing properties. We saw significant maturation only in increased spontaneous activity and decreased medium afterhyperpolarisation amplitude. Nor were adult-born dopaminergic cells especially plastic. In response to brief sensory deprivation via unilateral naris occlusion we observed no maturation-specific plastic alterations in intrinsic properties, although we did see deprivation-associated increases in spike speed and amplitude across all adult-born and resident neurons. Our results not only show that adult-born OB dopaminergic cells rapidly functionally resemble their pre-existing counterparts, but also underscore the importance of subtype identity when describing neuronal maturation and plasticity.
新神经元的持续整合仅在成年小鼠大脑的少数区域存在。在嗅球（OB）中，未成熟的成年新生神经元对嗅觉刺激的反应与更成熟的神经元不同，并且具有更高水平的活动依赖性可塑性。这些独特的功能特征被认为赋予了现有神经回路独特的特性。OB中间神经元，包括那些通过成年神经发生产生的中间神经元，由一组高度不同的亚型组成。然而，我们目前尚不清楚其功能发育和可塑性潜力背后不同的细胞类型特异性机制。在这里，我们专门研究了成年新生OB神经元的一个单一、明确亚型：多巴胺能细胞的电生理成熟和经验依赖性可塑性。我们选择性地对成年新生和“固有”多巴胺能细胞进行活体标记，并在急性小鼠OB切片中对它们进行全细胞膜片钳记录。令人惊讶的是，我们发现，从细胞年龄约1个月时能够首次可靠识别成年新生多巴胺能神经元开始，它们就已经具备了几乎完全成熟的内在放电特性。我们仅在自发活动增加和超极化后膜电位幅度减小方面观察到了显著的成熟。成年新生多巴胺能细胞也没有特别的可塑性。通过单侧鼻孔闭塞进行短暂感觉剥夺后，我们在内在特性方面未观察到成熟特异性的可塑性改变，尽管我们确实看到所有成年新生和固有神经元的动作电位速度和幅度都有与剥夺相关的增加。我们的结果不仅表明成年新生OB多巴胺能细胞在功能上迅速与其已有的对应细胞相似，还强调了在描述神经元成熟和可塑性时亚型身份的重要性。
