Cellular/Molecular
Mutated Glial Ca2+ Exchanger Underlies Seizure Phenotype
Jan E. Melom and J. Troy Littleton
(see pages 1169–1178)
Seizures are thought to involve reduced activity in inhibitory networks and increased activity in recurrent excitatory networks, often stemming from abnormalities in voltage-sensitive ion channels or GABAergic signaling. Although most research on seizure initiation and propagation focuses on neurons, glia may also have a role. Drosophila zydeco mutants undergo seizures when exposed to environmental stressors, and Melom and Littleton have mapped the mutation to an ion exchanger that extrudes cytosolic calcium. Surprisingly, zydeco was not expressed in neurons, but was restricted to a glial subtype called cortex glia, which encapsulate neuronal somata. Knockdown of zydeco selectively in cortex glia reproduced the seizure phenotype, whereas expressing wild-type zydeco in these cells rescued the phenotype. The function of cortex glia is unknown, but they exhibited calcium transients that were often restricted to microdomains surrounding single neurons. Such transients were absent in zydeco mutants, which had constitutively high calcium concentrations. The data suggest that disruption of glial calcium regulation underlies seizure susceptibility in zydeco mutants.
Zydeco (purple) is expressed in cortex glia, which surround neuron cell bodies in Drosophila CNS. Neuronal nuclei are green. See the article by Melom and Littleton for details.
Development/Plasticity/Repair
Some Low-Threshold Mechanoreceptors Are Shaped by Runx1
Shan Lou, Bo Duan, Linh Vong, Bradford B. Lowell, and Qiufu Ma
(see pages 870–882)
Most small-diameter, unmyelinated fibers (c-fibers) have high mechanical thresholds characteristic of nociceptors, but low-threshold mechanosensitive c-fibers (C-LTMRs) also exist. The function of C-LTMRs is unclear: although their low threshold suggests they sense light touch, knocking out the vesicular glutamate transporter they express—VGLUT3—produces abnormal pain responses, suggesting they contribute to nociception. Lou et al. report that VGLUT3 is expressed transiently in multiple subtypes of somatosensory neurons, but persists primarily in C-LTMRs that form lanceolate endings around hairs and in a small group of c-fibers that terminate like nociceptors, with free nerve endings in the skin. Fibers that persistently expressed VGLUT3 also expressed the transcription factor Runx1, and knocking out Runx1 in these cells prevented formation of lanceolate endings and reduced the number of mechanosensitive neurons in dorsal root ganglion cultures. Noxious mechanical, thermal, and chemical stimuli evoked normal pain behaviors in Runx1-null mice, however, suggesting that a different subset of neurons was responsible for the pain phenotype found in VGLUT3-null mice.
Systems/Circuits
Chronic Ethanol Increases EPSC Frequency in BNST Neurons
Yuval Silberman, Robert T. Matthews, and Danny G. Winder
(see pages 950–960)
Recovering drug addicts often relapse when faced with stress or contexts associated with drug use. In animals, reinstatement of drug seeking requires activation of the bed nucleus of the stria terminalis (BNST), a part of the extended amygdala. Stress-induced reinstatement requires release of norepinephrine and subsequent elevation of corticotropin releasing factor (CRF) in the BNST, resulting in activation of BNST neurons that project to the ventral tegmental area (VTA), which drives drug-seeking behaviors. Dopamine is involved in cue-induced reinstatement, but this pathway is poorly understood. Silberman et al. found that application of either dopamine or a β-adrenergic receptor agonist caused prolonged depolarization of CRF-expressing neurons in mouse BNST slices, and that CRF increased the frequency of spontaneous EPSCs in cells that projected to the VTA, likely by acting on CRF1 receptors on presynaptic neurons. Notably, repeatedly exposing mice to ethanol—a treatment that produces alcohol seeking—increased spontaneous EPSC frequency in VTA-projecting BNST neurons, and this effect was blocked by CRF1 receptor antagonist.
Behavioral/Cognitive
Saccadic Suppression Results from Rapid Image Motion
Michael Dorr and Peter J. Bex
(see pages 1211–1217)
Because visual acuity is much higher in the fovea than in the peripheral retina, primates continually make saccades to view points of interest with high resolution. To generate a stable representation of the world, the brain stitches together the images obtained during fixations and eliminates self-induced motion generated during saccades. Experiments using simple visual stimuli and highly controlled eye movements indicate that visual sensitivity is reduced during saccades. But whether this loss of sensitivity results from active suppression of visual input or simply from an inability to process rapidly changing visual stimuli has been debated. To address this, Dorr and Bex had people view nature videos and tested their ability to detect stimuli presented first during natural saccades, and then as the image was shifted to mimic the previous saccades. Sensitivity decreases were similar for active and passive saccades, indicating that perisaccadic sensitivity loss does not result from active suppression, but rather is a direct consequence of rapid movement of images across the retina.
