Ghatpande Ambarish S, Gelperin Alan
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
J Neurophysiol. 2009 Apr;101(4):2052-61. doi: 10.1152/jn.90734.2008. Epub 2009 Feb 18.
The mammalian olfactory bulb receives multiple modulatory inputs, including a cholinergic input from the basal forebrain. Understanding the functional roles played by the cholinergic input requires an understanding of the cellular mechanisms it modulates. In an in vitro olfactory bulb slice preparation we demonstrate cholinergic muscarinic modulation of glutamate release onto granule cells that results in gamma-aminobutyric acid (GABA) release onto mitral/tufted cells. We demonstrate that the broad-spectrum cholinergic agonist carbachol triggers glutamate release from mitral/tufted cells that activates both AMPA and NMDA receptors on granule cells. Activation of the granule cell glutamate receptors leads to calcium influx through voltage-gated calcium channels, resulting in spike-independent, asynchronous GABA release at reciprocal dendrodendritic synapses that granule cells form with mitral/tufted cells. This cholinergic modulation of glutamate release persists through much of postnatal bulbar development, suggesting a functional role for cholinergic inputs from the basal forebrain in bulbar processing of olfactory inputs and possibly in postnatal development of the olfactory bulb.
哺乳动物的嗅球接收多种调节性输入，包括来自基底前脑的胆碱能输入。要了解胆碱能输入所起的功能作用，需要了解其调节的细胞机制。在体外嗅球切片制备中，我们证明了胆碱能毒蕈碱对释放到颗粒细胞上的谷氨酸的调节作用，这导致γ-氨基丁酸（GABA）释放到二尖瓣/簇状细胞上。我们证明，广谱胆碱能激动剂卡巴胆碱触发二尖瓣/簇状细胞释放谷氨酸，从而激活颗粒细胞上的AMPA和NMDA受体。颗粒细胞谷氨酸受体的激活导致钙通过电压门控钙通道流入，从而在颗粒细胞与二尖瓣/簇状细胞形成的相互树突-树突突触处引发不依赖于动作电位的异步GABA释放。这种对谷氨酸释放的胆碱能调节在出生后嗅球的大部分发育过程中持续存在，这表明基底前脑的胆碱能输入在嗅球对嗅觉输入的处理中以及可能在嗅球的出生后发育中具有功能作用。
