Cellular/Molecular
Another Role for the M Current
Jérôme J. Devaux, Kleopas A. Kleopa, Edward C. Cooper, and Steven S. Scherer (see pages 1236–1244)
The subunits underlying the M current, a subthreshold potassium current first described in sympathetic neurons and pyramidal cells, evaded identification until the discovery of the KCNQ family a few years ago. KCNQ mutations are associated with several diseases, including epilepsy, hearing loss, and most recently, myokymia, a worm-like, repetitive movement of muscles thought to be attributable to axonal hyperexcitability. Devaux et al. now reveal expression of KCNQ2 in a location that might help explain these effects on neuronal excitability: initial segments and nodes of Ranvier in peripheral and central neurons. Aware of a slowly activating, M-like current at nodes, the authors searched for KCNQ subunits. They found KCNQ2 channels at nodes and initial segments, along with voltage-dependent sodium channels, and ankyrin-G, a cytoskeletal linker protein. KCNQ3 channels, in contrast, were expressed in a more diffuse, nonoverlapping pattern. The channels were seen only in nonfixed neurons, perhaps explaining past failures to detect the channels in nodes.
KCNQ2 (red) localizes to the axonal membrane at a node of Ranvier as seen in this single confocal section. The neurofilament protein, NF-H (green) marks the axonal cytoplasm.
Development/Plasticity/Repair
Making Renshaw Cells
Tamar Sapir, Eric J. Geiman, Zhi Wang, Tomoko Velasquez, Sachiko Mitsui, Yoshihiro Yoshihara, Eric Frank, Francisco J. Alvarez, and Martyn Goulding (see pages 1255–1264)
The Renshaw cell of the ventral spinal cord was the first physiologically identified interneuron, providing recurrent inhibition onto motor neurons. Now Sapir et al. reveal a bit of the path leading to Renshaw cell development. The neuronal circuits that control posture and locomotion in the ventral spinal cord arise from five embryonic precursors: motor neurons and four interneuron subtypes (V0–V3). In an effort to match up these embryonic interneurons with their mature fate, Sapir et al. concentrated on the V1 class. They first identified differentiated progeny of V1 cells expressing the En1 transcription factor, and determined that a subset of these were Renshaw cells. They then examined mice deficient in either of two transcription factors, Pax6 and En1. Pax6-deficient mice lacked Renshaw cells, whereas En1-deficient mice had Renshaw cells with fewer recurrent connections onto motor neurons, suggesting roles at different stages in Renshaw cell development.
Behavioral/Systems/Cognitive
Premotor Cortex Pathways that Shape the Hand
H. Shimazu, M. A. Maier, G. Cerri, P. A. Kirkwood, and R. N. Lemon (see pages 1200–1211)
Area F5 of the ventral premotor cortex is involved in the sensorimotor transformation that allows visually guided control of hand shape in activities such as grasping. Disruption of F5 activity interferes with hand grasping, and direct stimulation of F5 can evoke hand movements. Now Shimazu et al. examine whether F5 influences hand shape through direct connections to spinal cord or through corticocortical connections to primary motor cortex (M1). In anesthetized monkeys, stimulation of microelectrodes implanted in F5 did not produce direct corticospinal activity, although pairs of shocks did produce small, longer-latency (“indirect”) activity. Conditioning shocks to F5, however, facilitated M1-stimulated indirect corticospinal activity as well as EPSPs in hand motor neurons. The results point to an excitatory influence of area F5 on M1, presumably via activation of interneuronal networks in M1. The authors suggest that this mechanism may parallel the positive gain control of smooth pursuit eye movements mediated by frontal pursuit areas.
Neurobiology of Disease
The Timing of Stroke Rehab in the Rat
Jeff Biernaskie, Garry Chernenko, and Dale Corbett (see pages 1245–1254)
Clinicians know that strokes generally cause maximum functional deficits within a day or two of onset, followed often by gradual improvement that plateaus after a month or so. Although rehabilitation has many benefits, its effect on objective neurological recovery is difficult to measure in patients. In this issue, Biernaskie et al. investigated when rehabilitative training has the greatest impact. The authors occluded a middle cerebral artery (MCA) in rats to produce focal ischemia, followed by 5 weeks of rehabilitation at 5, 14, or 30 d after infarct. What is “rehab” in a rat? Well, cage objects were used to stimulate bimanual limb use, and reaching tasks encouraged use of the affected limb with mini M&Ms as the reward! Only the early treatment improved functional recovery. Interestingly, early rehab was also associated with increased length and branching of dendrites in layer V motor cortex in the undamaged hemisphere, indicating a possible role of rehabilitation on compensatory recruitment and remodeling.
