Dichotomous Anatomical Properties of Adult Striatal Medium Spiny Neurons

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Abstract
Principal medium spiny projection neurons (MSNs) of the striatum have long been thought to be homogeneous in their somatodendritic morphology and physiology. Recent work using transgenic mice, in which the two major classes of MSN are labeled, has challenged this assumption. To explore the basis for this difference, D1and D2receptor-expressing MSNs (D1and D2MSNs) in brain slices from adult transgenic mice were characterized electrophysiologically and anatomically. These studies revealed that D1MSNs were less excitable than D2MSNs over a broad range of developmental time points. Although M1muscarinic receptor signaling was a factor, it was not sufficient to explain the dichotomy between D1and D2MSNs. Reconstructions of biocytin-filled MSNs revealed that the physiological divergence was paralleled by a divergence in total dendritic area. Experimentally grounded simulations suggested that the dichotomy in MSN dendritic area was a major contributor to the dichotomy in electrophysiological properties. Thus, rather than being an intrinsically homogenous population, striatal MSNs have dichotomous somatodendritic properties that mirror differences in their network connections and biochemistry.