Similarly, the activity of an orthologous spinal microcircuit may be responsible for the grasp reflex in the human infant. Human fetuses develop a grasp reflex in the first trimester (Hooker, 1938) that persists in the postnatal period for 2−6 months (Halverson, 1937; Pollack, 1960). Reflexive grasping is not normally seen in adult humans, most likely because

find more higher systems regulate this microcircuit, which may also be involved in feed-forward control of hand function (see Rushworth and Denny-Brown, 1959). Presumably, these reflexes disappear because of the development of the brain and descending systems. Grasp reflexes emerge in adults with structural brain (Walshe and Hunt, 1936) and neurodegenerative diseases and their pathological reemergence can be quite disabling for both hand (Mestre and Lang, 2010) and foot function (Paulson and Gottlieb, 1968). In addition, the opposite effect—a loss of normal control of hand grasp, resulting, for example, from spinal cord injury—is significantly disabling (Anderson, 2004). Understanding dI3 INs and their control will aid in the development of microcircuit-targeted therapies to improve hand dysfunction in disease or following injury. Perifosine mw Expression of YFP driven

by the promoter for the homeodomain transcription factor Isl1 was obtained in double transgenic offspring of Isl1+/Cre and Thy1-lox-stop-lox-YFP mice. The following strains of mice were generously donated and used in this study: Thy1-lox-stop-lox-YFP mice (from J. Sanes) and Thy1-lox-stop-lox-mGFP (from S. Arber). Conditional knockout of vGluT2 Farnesyltransferase in Isl1-expressing neurons (dI3OFF) was accomplished by crossing

Isl1+/Cre mice with a strain of mice bearing a conditional allele of the Slc17a6 (vGluT2) gene where exon 2 of the gene was flanked by loxP sequences (vGluT2flox/flox; Figure 5A). This resulted in Cre-mediated excision of exon 2 of the vGluT2 gene in Isl1-expressing neurons ( Hnasko et al., 2010). All animal procedures were approved by the University Committee on Laboratory Animals of Dalhousie University and conform to the guidelines put forth by the Canadian Council for Animal Care. Additional methodological details can be found in Supplemental Information. Sagittal hemicords were prepared from Isl1-YFP or dI3OFF postnatal (P5–P16) mice. After anesthesia was administered by an injection of a mixture of xylazine and ketamine, mice were decapitated, and spinal cords were isolated by vertebrectomy in room temperature recording artificial cerebrospinal fluid (ACSF) (NaCl, 127 mM; KCl, 3 mM; NaH2PO4, 1.2 mM; MgCl2, 1 mM; CaCl2, 2 mM; NaHCO3, 26 mM; D-glucose, 10 mM). Ventral and dorsal roots were dissected as distally as possible. Cords were hemisected by a midline longitudinal incision, incubated for 45–60 min in 37°C recording ACSF, and equilibrated in room temperature recording ACSF for at least 30 min.