We provide evidence for a dichotomous functional organization of GPe that is as compelling as that in striatum. Because all vertebrate brains likely have (homologs of) both striatum and pallidum (Stephenson-Jones et al., 2011), one intriguing possibility is that functional duality co-evolved across the striato-pallidal axis. Given our new findings, GPe circuits are realistically viewed not as a single, homogeneous entity but as two interacting systems that engage in a division of labor to orchestrate both normal and abnormal activities across PF-06463922 mw the entire basal

ganglia. Experimental procedures were carried out on adult male Sprague-Dawley rats (Charles River), and were conducted in accordance with the United Kingdom Animals

(Scientific Procedures) Act, 1986. See Supplemental Experimental Procedures for further details. Unilateral 6-hydroxydopamine SB431542 purchase (6-OHDA) lesions were induced in 190–305 g rats, as described previously (Mallet et al., 2008a and Mallet et al., 2008b). All animals received desipramine (25 mg/kg, i.p.; Sigma) to minimize the uptake of 6-OHDA by noradrenergic neurons (Schwarting and Huston, 1996b). Lesions were assessed after 6-OHDA injection by challenge with apomorphine (0.05 mg/kg, s.c.; Sigma) (Schwarting and Huston, 1996a). Electrophysiological recordings were carried out in the GPe ipsilateral to 6-OHDA lesions in anesthetized rats 21–45 days after surgery. Recording and labeling experiments were performed in 45 anesthetized 6-OHDA-lesioned rats (271–540 g at the time of recording). Anesthesia was maintained with urethane (1.3 g/kg, i.p.), and supplemental doses of ketamine (30 mg/kg, i.p.) and xylazine (3 mg/kg, i.p.), as described previously (Mallet et al., 2008a and Mallet et al., 2008b). The epidural ECoG was recorded above the frontal (somatic sensory-motor) cortex (Mallet et al., 2008a). Extracellular recordings of single-unit activity in the GPe were made using glass electrodes (11–29 MΩ in situ; tip diameter ∼1.2 μm) containing 0.5 M NaCl solution and neurobiotin

(1.5% w/v; Vector Laboratories). Following electrophysiological through recordings, single neurons were juxtacellularly labeled with neurobiotin (Magill et al., 2001, Mallet et al., 2008a and Pinault, 1996). Seventy-nine individual GPe neurons were juxtacellularly labeled in this study. Parasagittal sections (50 μm) were cut from each perfusion-fixed brain and incubated overnight in Cy3-conjugated streptavidin. Sections containing neurobiotin-labeled neuronal somata (those marked with Cy3) were then isolated for molecular characterization by indirect immunofluorescence. All identified GPe neurons were tested for expression of parvalbumin (PV), and some were also tested for choline acetyltransferase (ChAT) and/or preproenkephalin (PPE).