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

多巴胺能和成人产生的谷氨酸能中间神经元在小鼠嗅球中的功能作用

• 批准号: 190796601
• 负责人: Professorin Dr. Magdalena Götz
• 金额: --
• 依托单位: Institut für Physiologische Genomik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/190796601?language=en
• 关键词: Functional; role; dopaminergic; adult; generated

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.

嗅觉系统是成年哺乳动物大脑中少数几个表现出持续终身神经发生的区域之一。嗅球（OB）的成体生成神经元出生在成人室下区（SVZ），并迁移到吻侧迁移流（RMS）到OB，在那里它们分化为OB中间神经元的特定亚型、颗粒神经元和肾小球周围神经元（PGNs）的亚型。然而，这些神经元亚型的具体作用及其终身新添加到OB网络尚不清楚。为了阐明这些特定的新生成的神经元亚型在成人嗅觉系统中持续整合的作用，我们将检查肾小球周围中间神经元PGNs的多巴胺能亚群，以及成人生成的谷氨酸能神经元，PGNs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数量的后果。利用不同的小鼠突变体和诱导遗传方法，我们将减少或完全消除多巴胺能PGNs或选择性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的理解，以及它们在成年动物中整合的具体贡献。

项目成果

Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

• DOI: 10.1073/pnas.1218991110
• 发表时间: 2013-03-19
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Deshpande, Aditi;Bergami, Matteo;Berninger, Benedikt
• 通讯作者: Berninger, Benedikt

Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb

• DOI: 10.1242/dev.097295
• 发表时间: 2014-01-01
• 期刊: DEVELOPMENT
• 影响因子: 4.6
• 作者: Agoston, Zsuzsa;Heine, Peer;Schulte, Dorothea
• 通讯作者: Schulte, Dorothea