Department of Psychiatry and Pharmacology, Columbia University, New York, NY 10032, USA.
J Neurosci. 2011 Jan 26;31(4):1183-92. doi: 10.1523/JNEUROSCI.3833-10.2011.
Dopamine system disorders ranging from movement disorders to addiction and schizophrenia involve striatal medium spiny neurons (MSNs), yet their functional connectivity has been difficult to determine comprehensively. We generated a mouse with conditional channelrhodopsin-2 expression restricted to medium spiny neurons and assessed the specificity and strength of their intrinsic connections in the striatum and their projections to the globus pallidus and the substantia nigra. In the striatum, medium spiny neurons connected with other MSNs and tonically active cholinergic interneurons, but not with fast-spiking GABA interneurons. In the globus pallidus, medium spiny neurons connected strongly with one class of electrophysiologically identified neurons, but weakly with the other. In the substantia nigra, medium spiny neurons connected strongly with GABA, but not with dopamine neurons. Projections to the globus pallidus showed solely D2-mediated presynaptic inhibition, whereas projections to the substantia nigra showed solely D1-mediated presynaptic facilitation. This optogenetic approach defines the functional connectome of the striatal medium spiny neuron.
多巴胺系统紊乱，从运动障碍到成瘾和精神分裂症，都涉及纹状体中间神经元（MSNs），但其功能连接一直难以全面确定。我们生成了一种条件性表达通道视紫红质-2的小鼠，该蛋白仅在中间神经元中表达，并评估了它们在纹状体中的内在连接的特异性和强度，以及它们对苍白球和黑质的投射。在纹状体中，中间神经元与其他 MSNs 和持续激活的胆碱能中间神经元连接，但不与快速放电 GABA 中间神经元连接。在苍白球中，中间神经元与一类电生理鉴定的神经元强烈连接，但与另一类神经元弱连接。在黑质中，中间神经元与 GABA 强烈连接，但与多巴胺神经元不连接。向苍白球的投射仅显示 D2 介导的突触前抑制，而向黑质的投射仅显示 D1 介导的突触前易化。这种光遗传学方法定义了纹状体中间神经元的功能连接组。
