Functional role of dopaminergic and adult generated glutamatergic interneurons in the mouse olfactory bulb

嗅觉系统是成年哺乳动物大脑中为数不多的显示持续终生神经发生的区域之一。成体嗅球(OB)神经元出生于成体脑室下带(SVZ)，迁移到OB的吻侧迁移流(RMS)，在那里分化为OB中间神经元、颗粒神经元和球周神经元(PGN)的特定亚型。然而，这些神经元亚型的具体作用以及它们对OB网络的终身新添加尚不清楚。为了阐明这些特定的新产生的神经元亚型的持续整合对成年嗅觉系统的作用，我们将研究肾小球周围中间神经元的多巴胺能亚群和成年产生的谷氨酸能神经元，这是PGN的另一个亚群。我们将一方面研究c-fos在特定嗅觉刺激下对这些神经元的激活，另一方面研究在行为水平上操纵这些特定中间神经元的数量的后果。使用不同的小鼠突变体和可诱导的遗传方法，我们将减少或完全消除多巴胺能PGN，或选择性地沉默成人产生的谷氨酸能OB中间神经元。这些方法将提高我们对这些中间神经元对嗅觉行为的一般功能以及它们在成年动物中整合的具体贡献的理解。

The olfactory system is one of the few areas in the adult mammalian brain that exhibit continuing life-long neurogenesis. The adult-generated neurons of the olfactory bulb (OB) are born in the adult subventricular zone (SVZ) and migrate into the rostral migratory stream (RMS) to the OB where they differentiate into specific subtypes of OB interneurons, granule neurons and subtypes of periglomerular neurons (PGNs). However, the specific role of these neuronal subtypes and their life-long new addition to the network of the OB is not known. To clarify the role of the continuous integration of these specific newly generated neuronal subtypes for the adult olfactory system we will examine the dopaminergic subset of periglomerular interneurons PGNs, and the adult-generated glutamatergic neurons, another subset of PGNs. We shall examine on the one hand the activation of these neurons by c-fos upon specific olfactory stimuli and on the other hand the consequences of manipulating the numbers of these specific interneurons at the behavioural level. Using different mouse mutants and inducible genetic approaches we will reduce or completely abolish dopaminergic PGNs or selectively silence adult-generated glutamatergic OB interneurons. These approaches will improve our understanding of the general function of these interneurons for olfactory behaviour as well as the specific contribution of their integration in the adult animal.