Striosome-based map of the mouse striatum that is conformable to both cortical afferent topography and uneven distributions of dopamine D1 and D2 receptor-expressing cells

Abstract

The striatum is critically involved in execution of appropriate behaviors, but its internal structures remain unmapped due to its unique structural organization, leading to ambiguity when interpreting heterogeneous properties of striatal neurons that differ by location. We focused on site-specific diversity of striosomes/matrix compartmentalization to draw the striatum map. Five types of striosomes were discriminated according to diverse immunoreactivities for the µ-opioid receptor, substance P (SP) and enkephalin, and each type occupied a particular domain inside the striatum. Furthermore, there was an additional domain lacking striosomes. This striosome-free space was located at the dorsolateral region and received afferents preferentially from the primary motor and sensory cortices, whereas the striosome-rich part received afferents from associational/limbic cortices, with topography inside both innervations. The proportion of dopamine D1 receptor-expressing, presumptive striatonigral neurons was approximately 70% in SP-positive striosomes, 40% in SP-deficient striosomes, 30% in the striosome-free space, and 50% in the matrix. In contrast, the proportion of D2 receptor-expressing, presumptive striatopallidal neurons was complementary to that of D1 receptor-expressing cells, indicating a close relationship between the map and the direct and indirect parallel circuitry. Finally, the most caudal part of the striatum lacked compartmentalization and consisted of three lamina characterized by intense and mutually exclusive immunoreactivities for SP and enkephalin. This tri-laminar part also received specific afferents from the cortex. The newly obtained map will facilitate broad fields of research in the basal ganglia with higher resolution of the three-dimensional anatomy of the striatum.Electronic supplementary materialThe online version of this article (10.1007/s00429-018-1749-3) contains supplementary material, which is available to authorized users.

Compartmental function and modulation of the striatum

“…Supporting this observation, single-cell tracing studies of striosome SPNs have reported higher percentages of neurons with axonal projections to basal ganglia output structures than to intermediate nuclei (Fujiyama et al, 2011;Levesque & Parent, 2005). Indeed, SP-rich striosomes (which are primarily found in the medial striatum in rodents) may contain up to 70% dSPNs, but the percentage of dSPNs is far lower (as low as 40%) in other striosome regions (Miyamoto et al, 2018). This dogma, however, should be qualified.…”

“…For example, acetylcholinesterase-poor regions (striosomes/patches) also express high levels of the µ-opioid receptor (MOR), while acetylcholinesterase-rich regions (matrix) express high levels of the Ca 2+ -binding protein calbindin (Herkenham & Pert, 1981;Pert et al, 1976). In general, the relative expression of dSPN-specific proteins is higher in striosomes and iSPN-specific proteins are higher in the matrix (Fujiyama et al, 2011;Guttenberg, Klop, Minami, Satoh, & Voorn, 1996;Levesque & Parent, 2005;Miyamoto et al, 2018). In general, the relative expression of dSPN-specific proteins is higher in striosomes and iSPN-specific proteins are higher in the matrix (Fujiyama et al, 2011;Guttenberg, Klop, Minami, Satoh, & Voorn, 1996;Levesque & Parent, 2005;Miyamoto et al, 2018).…”

“…In general, the relative expression of dSPN-specific proteins is higher in striosomes and iSPN-specific proteins are higher in the matrix (Fujiyama et al, 2011;Guttenberg, Klop, Minami, Satoh, & Voorn, 1996;Levesque & Parent, 2005;Miyamoto et al, 2018). Second, Miyamoto and colleagues recently demonstrated that striosomes can be classified into five types based on MOR, SP, and ENK expression, suggesting that there may be heterogeneity in both striosome function and their primary pathway-associated targets (Miyamoto et al, 2018). This has led to an oft-cited dogma that striosomes are predominantly composed of dSPNs.…”

“…Numerous other striatal proteins and genes are preferentially expressed in striosomes versus matrix-exhaustive lists are available elsewhere (Brimblecombe & Cragg, 2017;Crittenden & Graybiel, 2011). In general, the relative expression of dSPN-specific proteins is higher in striosomes and iSPN-specific proteins are higher in the matrix (Fujiyama et al, 2011;Guttenberg, Klop, Minami, Satoh, & Voorn, 1996;Levesque & Parent, 2005;Miyamoto et al, 2018). Supporting this observation, single-cell tracing studies of striosome SPNs have reported higher percentages of neurons with axonal projections to basal ganglia output structures than to intermediate nuclei (Fujiyama et al, 2011;Levesque & Parent, 2005).…”

“…Both compartments contain dSPNs and iSPNs, but the compartmental activities of these SPNs have been associated with distinct behaviors. For example, while striosomes only occupy about 10%-15% of the total striatal volume (Davis & Puhl, 2011;Desban, Kemel, Glowinski, & Gauchy, 1993;Johnston, Gerfen, Haber, & van der Kooy, 1990;Miyamoto, Katayama, Shigematsu, Nishi, & Fukuda, 2018;Morigaki & Goto, 2016), engagement of neurons within these compartments has been linked to the generation of drug-induced motor stereotypies, the selection of high-cost/ high-value reward options, and encoding expected outcomes during learning (Amemori et al, 2011;Bloem, Huda, Sur, & Graybiel, 2017;Canales & Graybiel, 2000;Friedman et al, 2015;Yoshizawa, Ito, & Doya, 2018).…”