Abstract
Striosomes were discovered several decades ago as neurochemically identified zones in the striatum, yet technical hurdles have hampered the study of the functions of these striatal compartments. Here we used 2-photon calcium imaging in neuronal birthdate-labeled Mash1-CreER;Ai14 mice to image simultaneously the activity of striosomal and matrix neurons as mice performed an auditory conditioning task. With this method, we identified circumscribed zones of tdTomato-labeled neuropil that correspond to striosomes as verified immunohistochemically. Neurons in both striosomes and matrix responded to reward-predicting cues and were active during or after consummatory licking. However, we found quantitative differences in response strength: striosomal neurons fired more to reward-predicting cues and encoded more information about expected outcome as mice learned the task, whereas matrix neurons were more strongly modulated by recent reward history. These findings open the possibility of harnessing in vivo imaging to determine the contributions of striosomes and matrix to striatal circuit function.
Highlights
We found strong tdTomato labeling of striosomes in the striatal regions of the caudoputamen that we examined (Figure 1, Figure 1—figure supplement 1). This labeling marked the cell bodies of the striosomal neurons, and their local processes, which were confined to the neuropil as confirmed histologically in initial immunohistochemical experiments (Figure 1). These experiments demonstrated that the clusters of labeled neurons and their neuropil corresponded to striosomes, as evidenced by the close match between the zones of tdTomato neuropil labeling and mu-opioid receptor 1 (MOR1)-rich immunostaining (Table 1) (Kelly et al, 2017; Tajima and Fukuda, 2013)
Our findings demonstrate that 2-photon calcium imaging can be used to identify the activity patterns of subpopulations of neurons distinguished as being in either the striosome or matrix compartments of the striatum
Even with the use of a simple classical conditioning task involving cues predicting high or low probabilities of receiving reward, we could detect in all mice many taskrelated striatal neurons, altogether 38% of the 2704 neurons successfully imaged in the post-training phase
Summary
The striatum, despite its relatively homogeneous appearance in simple cell stains, is made up of a mosaic of macroscopic zones, the striosomes and matrix, which differ in their input and output connections and are thought to allow specialized processing by physically modular groupings of striatal neurons (Crittenden et al, 2016; Fujiyama et al, 2011; Gerfen, 1984; Graybiel and Ragsdale, 1978; Jimenez-Castellanos and Graybiel, 1989; Langer and Graybiel, 1989; Lopez-Huerta et al, 2016; Salinas et al, 2016; Smith et al, 2016; Stephenson-Jones et al, 2016; Walker et al, 1993; Watabe-Uchida et al, 2012). The matrix and its constituent matrisomes receive abundant input from sensorimotor and associative parts of the neocortex (Flaherty and Graybiel, 1994; Gerfen, 1984; Parthasarathy et al, 1992; Ragsdale and Graybiel, 1990), and project via the main direct and indirect pathways to the pallidum and non-dopaminergic pars reticulata of the substantia nigra (Flaherty and Graybiel, 1994; Gimenez-Amaya and Graybiel, 1991; Kreitzer and Malenka, 2008), universally thought to modulate movement control (Albin et al, 1989; Alexander and Crutcher, 1990; DeLong, 1990)
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