Cellular/Molecular
Direction Selectivity Map Exists in Adult Barrel Cortex
Yves Kremer, Jean-François Léger, Dan Goodman, Romain Brette, and Laurent Bourdieu
(see pages 10689–10700)
Orderly mapping of response properties exists in sensory cortex. In rodents, the barrel cortex maps the facial whisker pad, with each vibrissa represented by a single barrel. Within the cortical map of the visual field, properties such as preferred orientation are organized on a finer spatial scale. Because rats whisk objects for identification and navigation, one might expect the barrel cortex to have an orderly mapping of whisker-direction selectivity analogous to the mapping of orientation selectivity in visual cortex. Electrophysiological recordings have provided evidence for such a map, but two-photon imaging has not. Kremer et al. suggest this discrepancy resulted from age differences in studies using the different approaches. They found that although neurons in young barrel cortex showed directional tuning, there was no apparent spatial organization for preferred direction. In contrast, a direction selectivity map was apparent in year-old rats, with neurons preferring deflection toward a nearby vibrissa usually located near the corresponding barrel.
Development/Plasticity/Repair
Motor Circuit Development Requires Patterned Activity
Sarah J. Crisp, Jan Felix Evers, and Michael Bate
(see pages 10445–10450)
Many developing sensory circuits rely on patterned activity to sculpt connections and refine maps. Developing motor circuits exhibit spontaneous activity, but whether this is required for proper wiring is unknown. Crisp et al. investigated this question in Drosophila embryos, which initially have uncoordinated muscle contractions, but acquire left–right synchronized and anterior–posterior progressing contractions before hatching. Preventing synaptic transmission during this transition delayed the emergence of coordinated movements. Interestingly, preventing transmission for a smaller fraction of this period caused a correspondingly smaller delay in coordination, suggesting that a set period of uncoordinated activity is required for proper circuit formation. Muscle contraction was not required for coordination to develop, but sensory input was, and increasing sensory stimulation optogenetically accelerated the emergence of coordinated activity. Eliciting synchronous, unpatterned activity in all neurons, however, prevented the emergence of coordination, indicating that patterned activity is required for the coordinated circuit to mature.
Behavioral/Systems/Cognitive
Cdk5 Regulates Axon Initial Segment Length
Svetlana Trunova, Brian Baek, and Edward Giniger
(see pages 10451–10462)
Like many invertebrate neurons, Drosophila mushroom-body γ-neurons are unipolar: they possess one primary neurite from which dendritic and axonal segments emerge. Nonetheless, axonal and dendritic proteins are sorted appropriately. Trunova et al. noticed, however, that an ∼15 μm section of the primary neurite distal to the site of dendrite emergence was not labeled by axonal, dendritic, or synaptic markers. The region appeared to have a specialized F-actin cytoskeleton, and it was enriched in ankyrin, a protein that marks mammalian axon initial segments (AISs), suggesting it is a homologous structure. Indeed, the analogous region was previously shown to be the site of axon potential generation in other Drosophila neurons. The length of the AIS-like structure was regulated by cyclin-dependent kinase cdk5, a protein involved in axonal patterning and synaptic plasticity in mammals. Reducing cdk5 activity shortened the structure, whereas increasing cdk5 activity lengthened the region. If cdk5 similarly regulates the mammalian AIS, this may play a role in neuronal plasticity.
In the mushroom body of Drosophila larvae, a region (demarcated by arrows) of γ-neurons excludes both somatodendritic (left, green) and axonal (left, red) proteins. Ankyrin (right) is enriched in this area. See the article by Trunova et al. for details.
Neurobiology of Disease
Seizure-Induced VEGF Release Disrupts the Blood–Brain Barrier
Mélanie Morin-Brureau, Aurore Lebrun, Marie-Claude Rousset, Laurent Fagni, Joël Bockaert, et al.
(see pages 10677–10688)
Epileptic seizures can disrupt the blood–brain barrier, and subsequent leakage of serum proteins into the brain promotes further epileptiform activity. The blood–brain barrier is created by endothelial cells that are connected by tight junctions, which are maintained by astrocytic end feet that ensheath blood vessels. Morin-Brureau et al. found that induction of seizure-like events in organotypic rat hippocampal cultures by kainate application reduced expression of the tight-junction scaffolding protein zonula occludens (ZO-1). Levels of vascular endothelial growth factor (VEGF), which promotes angiogenesis and vascular permeability, also increased, as did vascular branching. Binding of VEGF to its receptor VEGFR-2 activates protein kinase C (PKC) and Src kinase. Inhibiting the former prevented the kainate-induced increase in branching, whereas inhibiting the latter prevented down-regulation of ZO-1. Because increased blood vascularization is potentially beneficial, whereas disrupting the blood–brain barrier is harmful, targeting VEGF-dependent Src signaling might improve outcomes after seizure.
