Medium spiny neuron

The axons of both pathways arise from the medium spiny neurons that constitute 80% of striatal cells. These neurons release GABA but those to the Ind Path have... 

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. 

FIGURE 56-7 Repeated exposure to amphetamine or cocaine increases spine density and the number of branched spines in medium spiny neurons, the major cell type of the nucleus accumbens. Left camera lucida drawings of representative dendritic segments. Rats received 20 injections of saline (S), amphetamine (A) or cocaine (C) over 4 weeks and were then left undisturbed for about 1 month prior to analysis. Adapted from Robinson, T. E. and Kolb, B., Eur. ]. Neurosci. 11 1598-1604, 1999. 

Using retrograde horseradish peroxidase, Grofova (1975) demonstrated that medium spiny neurons were... 

Tang T-S, Slow EJ, Lupu V, Stavrovskaya IG, Sugimori M, Llinas R, Kristal BS, Hayden MR, Bezprozvanny I (2005) Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington s disease. Proc Natl Acad Sci USA 102 2602—2607. 

Transmission from cortical glutamate neurons to striatal GABAergic medium spiny neurons is subject to long-term depression (LTD), a long-lasting decrease... 

Geldwert D, Norris JM, Feldman IG, Schulman JJ, Joyce MP, Rayport S (2006) Dopamine presy-naptically and heterogeneously modulates nucleus accumbens medium-spiny neuron GABA... 

Mizuno T, Schmauss C, Rayport S (2007) Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens. BMC Neurosci 8 8-23... 

Wang Z, Kai L, Day M, Ronesi J, Yin HH, Ding J, Tkatch T, Lovinger D, Surmeier DJ (2006) Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Neuron 50 443-52... 

Finally, whole-cell recordings of membrane potential from medium spiny neurons in nucleus accumbens of wild-type and 5-HT1B receptor knockout mice show that 5-HT1B receptor agonists inhibited glutamate-induced EPSC in wild-type, but not knockout, mice (165). 

Surmeier DJ, Ding J, Day M, Wang Z, Shen W. 2007. D1 and D2 dopamine-receptor modulation of striatal glutamater-gic signaling in striatal medium spiny neurons. Trends Neurosci 30 228-235. 

Surmeier DJ, Song W-J, Yan Z. 1996. Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci 16 6579-6591. 

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). 

Striatal medium spiny neurons express L, N, P, Q, T and R-type Ca2+ channels (Bargas et al., 1994 Churchill and Macvicar, 1998). D1 receptor stimulation increases voltage-dependent L-type Ca2+ currents (Surmeier et al., 1995) by a mechanism that is essentially the same as that demonstrated in cardiac myocyte and that results from a PKA-dependent phosphorylation of a and/or (I subunits of the channels (Kamp and Hell, 2000). This upregulation of L-type Ca2+ channel appears to play a major contribution in the ability of dopamine to facilitate NMDA effects in striatal neurons (Cepeda et al., 1998). 

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). 

Hernandez-Lopez S, Bargas J, Surmeier DJ, Reyes A, Galarraga E (1997) D1 receptor activation enhances evoked discharge in neostriatal medium spiny neurons by modulating an L-type Ca2+ conductance. J Neurosci 77 3334-3342. 

Hernandez-Lopez S, Tkatch T, Perez-Garci E, Galarraga E, Bargas J, Hamm H, Surmeier DJ (2000) D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]l-IP3-calcineurin-signaling cascade. J Neurosci 20 8987-8995. 

On the other hand D2 receptor stimulation in enkephalin-expressing medium spiny neurons suppresses Ca++ currents through L-type Ca++ channels (Hernandez-Lopez et al., 2000). Suppression is not mediated by inhibition of adenylate cyclase. 

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