Most brains were cut sagittally in order to better visualize striatonigral projection axons, as well as frontal cortex layer boundaries. However, some brains were instead cut coronally to better delineate cortical layer borders near the midline and in very lateral cortical regions. Tissue groups that were not used immediately were find more placed in a cryopreservative solution (30% glycerol, 30% ethylene glycol in PBS) and stored at −20°C. Fixed tissue was immunostained using a standard protocol. To preserve mCherry signal, we used a rabbit polyclonal antibody against DsRed (1:250, Clontech) and amplified with a Cy3-conjugated anti-rabbit secondary antibody (Jackson ImmunoResearch). To visualize cell bodies and perikarya, tissue was also labeled
with a fluorescent Nissl
stain (Neurotrace 500/525, Invitrogen) at 1:500 dilution in PBS for 15 min after immunostaining. Immunostained tissue was mounted on chrome-gelatin subbed slides and allowed to dry overnight. Tissue was then dehydrated and defatted using a series of ethanol and xylenes immersion steps. Slides were then coverslipped using Krystalon (Harleco, Gibbstown) mounting medium and glass coverslips. We would like to thank Liza Schoenfeld and Karine Von Bochmann for technical assistance, as well as Harvey Karten and David Kleinfeld for anatomical discussion and providing access to the Nanozoomer slide scanner. This work was supported by National Institutes of Health grants MH063912, NS064984, and DA010154, with additional support from the Gatsby Charitable Foundation. Capmatinib “
“Across the animal kingdom, and across the range from normal to dysfunctional states in humans, the balance between flexible and repetitive behaviors is critical for optimal performance of tasks (Aston-Jones and Cohen, 3-mercaptopyruvate sulfurtransferase 2005, Balleine et al., 2009, Brainard and Doupe, 2002, Daw et al., 2005, Graybiel, 2008, Hikosaka
and Isoda, 2010 and Yin and Knowlton, 2006). Flexible goal seeking is advantageous in many situations, but a narrowing of behavioral focus is necessary to reach specific goals. Conversely, fixed routines are advantageous in freeing up attention and decision-making resources, but habits can be harmful and difficult to break (Everitt and Robbins, 2005, Graybiel, 2008, Hyman et al., 2006, Kalivas and Volkow, 2005 and Redish et al., 2008). Classic experimental studies based on lesion and chemical inactivation methods have identified two major brain regions as being essential for performing habits in animal studies. One, the sensorimotor striatum (called the dorsolateral striatum, DLS, in rodents), is embedded in sensorimotor basal ganglia circuitry (McGeorge and Faull, 1989). This striatal region is thought to store action plans for habit learning based on its anatomical position, its neural activity related to behavioral responses, and evidence that damage to it disrupts the stability of well-honed behaviors (Aldridge et al., 2004, Balleine et al., 2009, Carelli et al., 1997, Graybiel, 2008, Kimchi et al.