Striatum medium spiny neurons

GABA is the predominant intrinsic transmitter of the basal ganglia. Inhibition and disinhibition are considered to be the most important modes of information transfer in the basal ganglia. Ninety-five percent of all neurons in the striatum are GABAergic medium spiny neurons. These neurons are the striatal output neurons. The medium spiny neurons which give rise to the direct pathway also contain substance P or dynorphin as a co-transmitter, while those striatal output neurons that give rise to the indirect pathway contain enkephalin as a co-transmitter. Most striatal interneurons, as well as neurons in GPe, GPi and SNr are also GABAergic. Because striatal and GPe... 

Dopamine acts on G-protein-coupled receptors belonging to the D1 -family of receptors (so-called D1-like receptors , or DlLRs, comprised of Dl- and D5-receptors), and the D2-family of receptors ( D2-like receptors , or D2LRs comprised of D2-, D3- and D4-receptors). Dl LRs stimulate adenylate cyclase activity and, possibly, also phosphoinosit-ide hydrolysis, while D2LRs reduce adenylate cyclase activity. In the striatum, DlLRs are predominately associated with medium spiny neurons of the direct pathway, while D2LRs have been found as autoreceptors on dopaminergic terminals, as heteroreceptors on cholinergic interneurons, and on indirect pathway neurons. In the SNr, DlLRs are located on terminals of the direct pathway projection, while D2LRs appear to function as autoreceptors. 

The ultrastructural organization of dopaminergic boutons in the striatum has been extensively investigated (see, inter alia, the reviews of Smith and Bolam, 1990 Sesack, 2003). Extrastriatal inputs, including the dopaminergic one, terminate mainly on the more distal part of the dendritic tree of medium spiny neurons, while intrinsic inputs terminate mainly on the proximal parts of the dendritic shaft and on the cell body. A small proportion of dopaminergic axons also contact the cell body of striatal projection neurons (Fig. 18B). 

Application of a D1 receptor agonist reduces GABA-evoked currents in neurons from the striatum or olfactory bulb (Brunig et al., 1999 Flores-Hernandez et al., 2000). This effect, in striatal medium spiny neurons, is mediated through the activation of PKA/DARPP-32/ PP-1 cascade, since it is blocked by an inhibitor of PKA or by the absence of DARPP-32 in mutant mice while it is mimicked by inhibitor of PP-1 (Flores-Hernandez et al., 2000). Stimulation of the D1 receptor induces a phosphorylation of (32/(33 GABAa... 

Early studies reported the lack of stimulation of PLC activity by D2 agonist in the striatum but the measures were taken in striatal slices in which D2 agonists could have very complex effects (Kelly et al., 1988 Pizzi et al., 1988 Rubinstein and Hitzemann, 1990). Mobilization of Ca2+ from intracellular stores by D2 receptor activation has been observed in striatal medium spiny neurons (Hernandez-Lopez et al., 2000). The medium spiny neurons express PLCpl and the D2 receptor activation could stimulate this enzyme by mobilizing Gpy subunits (Hernandez-Lopez et al., 2000). The elevation of intracellular Ca2+ in medium spiny neurons was very transient, since it promoted an immediate closure of L type-Ca2+ channels, due to the activation of the Ca2+-dependent protein phosphatase, calcineurin and subsequent dephosphorylation of the L-type Ca2+ channels (Hernandez-Lopez et al., 2000). 

Walsh JP (1991) Long-term potentiation (LTP) of the excitatory synaptic input to medium spiny neurons of the rat striatum. Soc Neurosci Abstr 17 852. 

Chen Q, Veenman L, Knopp K, Yan Z, Medina L, Song W-J, Surmeier DJ, Reiner A (1998a) Evidence for the preferential localization of glutamate receptor-1 subunits of AMPA receptors to the dendritic spines of medium spiny neurons in rat striatum. Neuroscience S5 749-761. 

CBi receptors are also expressed at low to moderate levels in the nucleus accumbens. Here CBi receptors are found in a pattern reminiscent of the striatum. CBi receptors are expressed on terminals of the glutamatergic prefrontal cortex accumbens pathways (Robbe et al. 2001). They are also present on the accumbens medium spiny neurons. They appear to be absent from the dopaminergic terminals projecting to the accumbens from the ventral tegmentum. Consequently, cannabinoid stimulation of dopamine release in nucleus accumbens (Tanda et al. 1997) appears to be an indirect effect, perhaps mediated by inhibition of GABA release (Szabo et al. 1999,2002). 

These latter studies have demonstrated that the dendrites may take tortuous paths to remain confined within a particular compartment. In particular, patch neurons are often seen to have recurved dendrites that dutifully respect the borders between the patch and matrix compartments. This organization of the dendrites of medium spiny neurons suggests that afferents from outside the striatum that target a particular compartment... 

Medium spiny neurons have a common morphology in terms of their size, dendritic organization and local axon collaterals. Within the striatum these neurons have an axon... 

Lin, J, Y Chung, K, K, de Castro, D Funk, G. D and Lipski, J. (2004), Effects of muscarinic acetylcholine receptor activation on membrane currents and intracellular messengers in medium spiny neurones of the rat striatum. nr, y. Neu>osci.20,1219-1230. 

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