中型多棘神经元

中型多棘神经元（英語：Medium spiny neurons，简称MSNs），也称纹状体棘状突起投射神经元（英語：spiny projection neurons，简称SPNs）是一种特殊的丙胺基丁酸神經元（英语：GABAergic）抑制性（英语：Inhibitory postsynaptic potential）细胞，人类体内纹状体（一种基底核）中，95%的神经元都是由这种细胞构成。中型多棘神经元拥有两种表型：D1类（英语：D1-type）中型多棘神经元（直接径路）和D2类（英语：D2-type）中型多棘神经元（间接径路）。 帕金森病异动症的突触可塑性机制及治疗策略研究. www.cjnm.net. [2017-07-05].  Yager LM, Garcia AF, Wunsch AM, Ferguson SM. The ins and outs of the striatum: Role in drug addiction. Neuroscience. August 2015, 301: 529–541. PMC 4523218 . PMID 26116518. doi:10.1016/j.neuroscience.2015.06.033. [The striatum] receives dopaminergic inputs from the ventral tegmental area (VTA) and the substantia nigra (SNr) and glutamatergic inputs from several areas, including the cortex, hippocampus, amygdala, and thalamus (Swanson, 1982; Phillipson and Griffiths, 1985; Finch, 1996; Groenewegen et al., 1999; Britt et al., 2012). These glutamatergic inputs make contact on the heads of dendritic spines of the striatal GABAergic medium spiny projection neurons (MSNs) whereas dopaminergic inputs synapse onto the spine neck, allowing for an important and complex interaction between these two inputs in modulation of MSN activity ... It should also be noted that there is a small population of neurons in the NAc that coexpress both D1 and D2 receptors, though this is largely restricted to the NAc shell (Bertran- Gonzalez et al., 2008). ... Neurons in the NAc core and NAc shell subdivisions also differ functionally. The NAc core is involved in the processing of conditioned stimuli whereas the NAc shell is more important in the processing of unconditioned stimuli; Classically, these two striatal MSN populations are thought to have opposing effects on basal ganglia output. Activation of the dMSNs causes a net excitation of the thalamus resulting in a positive cortical feedback loop; thereby acting as a ‘go’ signal to initiate behavior. Activation of the iMSNs, however, causes a net inhibition of thalamic activity resulting in a negative cortical feedback loop and therefore serves as a ‘brake’ to inhibit behavior ... there is also mounting evidence that iMSNs play a role in motivation and addiction (Lobo and Nestler, 2011; Grueter et al., 2013). For example, optogenetic activation of NAc core and shell iMSNs suppressed the development of a cocaine CPP whereas selective ablation of NAc core and shell iMSNs ... enhanced the development and the persistence of an amphetamine CPP (Durieux et al., 2009; Lobo et al., 2010). These findings suggest that iMSNs can bidirectionally modulate drug reward. ... Together these data suggest that iMSNs normally act to restrain drug-taking behavior and recruitment of these neurons may in fact be protective against the development of compulsive drug use.  Ferré S, Lluís C, Justinova Z, Quiroz C, Orru M, Navarro G, Canela EI, Franco R, Goldberg SR. Adenosine-cannabinoid receptor interactions. Implications for striatal function. Br. J. Pharmacol. June 2010, 160 (3): 443–453. PMC 2931547 . PMID 20590556. doi:10.1111/j.1476-5381.2010.00723.x. Two classes of MSNs, which are homogeneously distributed in the striatum, can be differentiated by their output connectivity and their expression of dopamine and adenosine receptors and neuropeptides. In the dorsal striatum (mostly represented by the nucleus caudate-putamen), enkephalinergic MSNs connect the striatum with the globus pallidus (lateral globus pallidus) and express the peptide enkephalin and a high density of dopamine D2 and adenosine A2A receptors (they also express adenosine A1 receptors), while dynorphinergic MSNs connect the striatum with the substantia nigra (pars compacta and reticulata) and the entopeduncular nucleus (medial globus pallidus) and express the peptides dynorphin and substance P and dopamine D1 and adenosine A1 but not A2A receptors (Ferréet al., 1997; Gerfen, 2004; Quiroz et al., 2009). These two different phenotypes of MSN are also present in the ventral striatum (mostly represented by the nucleus accumbens and the olfactory tubercle). However, although they are phenotypically equal to their dorsal counterparts, they have some differences in terms of connectivity. First, not only enkephalinergic but also dynorphinergic MSNs project to the ventral counterpart of the lateral globus pallidus, the ventral pallidum, which, in fact, has characteristics of both the lateral and medial globus pallidus in its afferent and efferent connectivity. In addition to the ventral pallidum, the medial globus pallidus and the substantia nigra-VTA, the ventral striatum sends projections to the extended amygdala, the lateral hypothalamus and the pedunculopontine tegmental nucleus. Finally, unlike the dorsal striatum, the substantia nigra pars reticulata is not a main target area for the ventral striatum, which preferentially directs its midbrain output to the substantia nigra pars compacta and the VTA (Heimer et al., 1995; Robertson and Jian, 1995; Ferré, 1997). It is also important to mention that a small percentage of MSNs have a mixed phenotype and express both D1 and D2 receptors (Surmeier et al., 1996). ... A2A receptors are localized predominantly postsynaptically in the dendritic spine of enkephalinergic but not dynorphinergic MSNs, co-localized with D2 receptors  ... Presynaptically, CB1 receptors are localized in GABAergic terminals of interneurons or collaterals from MSNs, and also in glutamatergic but not in dopaminergic terminals ... Postsynaptically, CB1 receptors are localized in the somatodendritic area of MSN (Rodriguez et al., 2001; Pickel et al., 2004; 2006; Köfalvi et al., 2005) and both enkephalinergic and dynorphinergic MSNs express CB1 receptors (Martín et al., 2008).  Nishi A, Kuroiwa M, Shuto T. Mechanisms for the modulation of dopamine d(1) receptor signaling in striatal neurons. Front Neuroanat. July 2011, 5: 43. PMC 3140648 . PMID 21811441. doi:10.3389/fnana.2011.00043. Dopamine plays critical roles in the regulation of psychomotor functions in the brain (Bromberg-Martin et al., 2010; Cools, 2011; Gerfen and Surmeier, 2011). The dopamine receptors are a superfamily of heptahelical G protein-coupled receptors, and are grouped into two categories, D1-like (D1, D5) and D2-like (D2, D3, D4) receptors, based on functional properties to stimulate adenylyl cyclase (AC) via Gs/olf and to inhibit AC via Gi/o, respectively ... It has been demonstrated that D1 receptors form the hetero-oligomer with D2 receptors, and that the D1–D2 receptor hetero-oligomer preferentially couples to Gq/PLC signaling (Rashid et al., 2007a,b). The expression of dopamine D1 and D2 receptors are largely segregated in direct and indirect pathway neurons in the dorsal striatum, respectively (Gerfen et al., 1990; Hersch et al., 1995; Heiman et al., 2008). However, some proportion of medium spiny neurons are known to expresses both D1 and D2 receptors (Hersch et al., 1995). Gene expression analysis using single cell RT-PCR technique estimated that 40% of medium spiny neurons express both D1 and D2 receptor mRNA (Surmeier et al., 1996).