Cellular/Molecular
Typing Nociceptors
Xin Fang, Laiche Djouhri, Simon McMullan, Carol Berry, Stephen G. Waxman, Kenji Okuse, and Sally N. Lawson
(see pages 7281–7292)
Nociceptive sensory neurons of the dorsal root ganglia (DRGs) are generally divided into two main subclasses: those that bind the plant isolectin-B4 (IB4) and those that express the nerve growth factor receptor tyrosine kinase A (trkA). However, this week Fang et al. argue that the situation is more complex after assessing a large sample of rat lumbar DRG neurons in vivo. The authors typed the DRGs in terms of size and staining intensity for IB4 and trkA, with results similar to those reported previously. They also filled individual neurons with fluorescent dye and determined their responsiveness to noxious and mechanical stimuli. Strongly IB4+ neurons were all C-type nociceptors, but approximately one-third of IB4+ neurons also expressed trkA. IB4+ neurons expressed the voltage-activated sodium channel Nav1.9 that may contribute to the electrophysiological properties that result in their broader action potentials and slow conduction velocities.
Development/Plasticity/Repair
Regenerating a Cerebellum
Reinhard W. Köster and Scott E. Fraser
(see pages 7293–7304)
The cerebellum arises from the anterior hindbrain according to signals from isthmic cells of the midbrain–hindbrain boundary (MHB). In this week's Journal, Köster and Fraser follow the remarkably plastic regeneration of cerebellar neurons after ablation. To track the neurons, the authors used transgenic zebrafish that expressed green fluorescent protein (GFP) in cerebellar precursor neurons of the upper rhombic lip. With in vivo time-lapse confocal microscopy, the authors watched these cells migrate toward the MHB, turn ventrally, and settle at the anteroventral base of rhombomere 1. When the cerebellum was ablated at 36 h after fertilization, GFP-labeled cells regenerated within a few days, and the fish were swimming and capturing prey normally at day 6. The regenerating cerebellar cells, derived from the remaining dorso-anterior hindbrain, expressed rhombic lip marker genes, and migrated and positioned themselves normally. The regeneration was dependent on FGF that originated in the remaining isthmic cells.
Behavioral/Systems/Cognitive
The Goals of Single Prefrontal Neurons
Aldo Genovesio, Peter J. Brasted, and Steven P. Wise
(see pages 7305–7316)
If you're having trouble setting goals, Genovesio et al. may be able to tell you where the problem resides. The authors examined prefrontal cortex (PF) neuronal activity in the encoding of previous and future goal selection. Monkeys were presented with three options for spatial goal selection, in the form of shapes on a video screen. In each trial, a complex visual cue accompanied the goals. On disappearance of the cue, the monkeys made a saccadic eye movement to the chosen goal. In each subsequent trial, the monkeys were trained to select a new spatial goal when the visual cue changed and to maintain the present goal when the visual cue was repeated. The authors found that discrete PF neuron populations were activated for previous versus future goals. Failure of these distinct networks that allow us to distinguish past and future goals means omissions, perseverations, and endless rechecking of previous tasks; sound familiar?
Neurobiology of Disease
Restorative Dopamine Treatment in Hemiparkinsonian Rats
Jackalina M. Van Kampen and Christopher B. Eckman
(see pages 7272–7280)
This week, Van Kampen and Eckman take a new angle on dopamine therapy: restoration rather than the usual chemical replacement approach. The authors examined the neurogenic effects of dopamine D3 receptor activation in hemiparkinsonian adult rats. The number of dopamine neurons in the SNC was greatly reduced 2 weeks after unilateral treatment with 6-hydroxydopamine. Subsequent intraventricular infusion of the D3 receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) led to proliferation of cells, some of which matured into dopaminergic neurons. After 8 weeks of treatment, the number of dopamine neurons and their nigrostriatal projections had recovered to ∼75% of those on the contralateral side. The rats displayed substantial behavioral recovery as well, as tested after a 3 d drug washout to prevent acute effects of the agonist. Using drug-induced rotational analysis, the authors observed improved locomotor asymmetry after 4–8 weeks of treatment with 7-OH-DPAT. Treated rats also improved their performance on a skilled reaching task.
The D3 agonist 7-OH-DPAT stimulated proliferation of cells in the subventricular zone as shown by bromodeoxyuridine immunolabeling (red) after intraventricular treatment (*) with saline (A) or 7-OH-DPAT (B). See Van Kampen and Eckman for details.
