To test this possibility, whole-cell recordings were taken from D2-eGFP BAC mice crossed with M1receptor knock-out mice (Shen et al., 2007). the dichotomy in MSN dendritic area was a major contributor to the dichotomy in electrophysiological properties. Therefore, rather than being an intrinsically homogenous human population, striatal MSNs have dichotomous somatodendritic properties that mirror variations in their network contacts and biochemistry. Keywords:medium spiny neuron, striatum, anatomical reconstruction, basal ganglia, excitability, whole-cell patch-clamp recording == Intro == A point of convergence for cortical and thalamic excitatory signals, the striatum is definitely thought to participate in a wide range of psychomotor behaviors (Ragsdale and Graybiel, 1981;Schultz, 2006;Balleine et al., 2007). The principal target of these signals is the GABAergic medium Etofylline spiny projection neuron (MSN). MSNs are commonly divided into two major subsets based on their manifestation of both releasable peptides and dopamine (DA) receptors, and their axonal projection focuses on (Gerfen and Young, 1988;Le Moine et al., 1991). MSNs with axonal projections to the substantia nigra pars reticulata (SNr) communicate compound P, dynorphin, and D1DA receptors (D1MSNs), whereas MSNs with principal axon projections to the globus pallidus communicate enkephalin and D2DA receptors (D2MSNs). Although less well characterized than the biochemical and anatomical variations, MSNs Etofylline also appear to differ in their synaptic connectivity. For example, striatal neurons have been divided into type I and II neurons based on Etofylline paired-pulse reactions to cortical activation, a feature attributable to variable striatal GABAergic interneuron connectivity (Gerfen and Adolescent, 1988). Even though correlation between these two response types and D1and D2MSNs has been suggested (Onn et al., 1994), it has not been founded. MSNs also differ in their activity level during cortically driven up-states in anesthetized rodents (Wickens and Wilson, 1998). As the cortical glutamatergic input to D1and D2MSNs appears to arise from unique projection systems (Lei et al., 2004), it is possible that variance in presynaptic sites and launch properties could account for the observed dichotomy, but again there is no obvious linkage with the D1and D2MSN phenotypes. Despite the dichotomies in axonal projections and synaptic connectivity, D1and D2MSNs have been thought of as homogenous in their somatodendritic morphology and intrinsic physiological properties. Until recently, distinguishing MSNs while recording has been theoretically hard and labor rigorous, requiring either single-cell gene profiling (Surmeier et al., 1996) or axonal tracing (Kawaguchi et al., 1990). The development of bacterial artificial chromosome (BAC) transgenic mice expressing enhanced green fluorescent PPARG protein (eGFP) under the control of promoters for the D1and D2receptors offers eliminated this problem (Day time et al., 2006;Wang et al., 2006;Kreitzer and Malenka, 2007;Shen et al., 2007;Ade et al., 2008;Cepeda et al., 2008). Based on work with BAC transgenic mice,Kreitzer and Malenka (2007)have suggested that in 3-week-old mice, D2MSNs are more responsive to intrasomatic current injection than are D1MSNs. To pursue this observation, whole-cell patch-clamp recordings were from recognized D1and D2MSNs in mind slices from BAC transgenic mice between 3 and 10 weeks of age. MSNs were characterized electrophysiologically, Etofylline filled with biocytin, and anatomically reconstructed. These studies confirmed that D2MSNs are more responsive to intrasomatic current injection, but more importantly provided an important clue as to why: D2MSNs experienced significantly smaller dendritic trees than did D1MSNs. Computer simulations suggested that this anatomical dichotomy was a major factor underlying the electrophysiological dichotomy. == Materials and Methods == == == == == == Slice preparation. == All experiments detailed are in accord with the Northwestern University or college Animal Care and Use Committee. D1and D2receptor-eGFP BAC transgenic mice on an FVB background, developed by the GENSAT project (Heintz, 2004), between postnatal days 3545 (unless normally indicated), were anesthetized with ketamine/xylazine and perfused transcardially with ice-cold artificial CSF (aCSF), comprising in mm: 125 NaCl, 2.5 KCl, 1.25 NaH2PO4, 2.0 CaCl2, 1.0 MgCl2, 25 NaHCO3, and 12.5 glucose, bubbled continuously with carbogen (95% O2and 5% CO2). The brains were rapidly eliminated, glued to the stage of a VT1000S slicer (Leica), and immersed in ice-cold.
To test this possibility, whole-cell recordings were taken from D2-eGFP BAC mice crossed with M1receptor knock-out mice (Shen et al