This Week in The Journal

Development/Plasticity/Repair

Terminal Schwann Cells Strip Synapses During Development

Ian W. Smith, Michelle Mikesh, Young il Lee, and Wesley J. Thompson

In the developing nervous system, targets often receive more inputs than they retain. Competition between innervating axons is thought to drive elimination of supernumerary inputs, after which degenerating axons are phagocytosed by glia. Now Smith et al. provide evidence that glia have a larger role in synapse elimination than previously appreciated. Reconstructions of early postnatal mouse neuromuscular junctions from serial electron micrographs revealed that muscle fibers were innervated by multiple motor neurons, all of which contacted a single plaque of acetylcholine receptors. Terminal Schwann cells (tSCs) enwrapped axon terminals, but also closely apposed receptor plaques, extending to plaque boundaries and covering more than twice the area contacted by axon terminals. Often, tSC processes extended between nerve terminals and muscle fibers. Some of these processes showed evidence of phagocytosis, suggesting tSCs actively remove synaptic contacts. Based on these images and previous computational models, the authors propose that tSCs promote synaptic turnover, which is sufficient to drive loss of all but one innervating axon.

Three-dimensional reconstruction of a tSC (green) penetrating an intact nerve terminal (blue) that contains synaptic vesicles (yellow) and is in contact with the postsynaptic muscle fiber (red). See the article by Smith et al. for details.

Systems/Circuits

On-Off Ganglion Cells Contribute to Image Stabilization

Onkar S. Dhande, Maureen E. Estevez, Lauren E. Quattrochi, Rana N. El-Danaf, Phong L. Nguyen, et al.

(see pages 17797–17813)

During head movements, the vestibular system drives compensatory eye movements to stabilize the image on the retina. During slow head movements, however, vestibular-driven compensation is imprecise, and the image slips across the retina. This retinal slip is detected by a specialized population of direction-sensitive retinal ganglion cells (DSGCs) that project to brainstem nuclei of the accessory optic system (AOS), which fine-tune compensatory eye movements. On-DSGCs, which have large receptive fields and respond best to slow movements, are thought to detect retinal slip. In contrast, On-Off DSGCs, which are tuned to faster movement, are thought to encode movement of objects in the world. But by examining mice expressing green fluorescent protein selectively in AOS-projecting RGCs, Dhande et al. discovered that ∼32% of these cells were On-Off DSGCs that were sensitive to motion in the temporal–nasal direction. Although these neurons were electrophysiologically and morphologically similar to other On-Off DSGCs, they were less strongly tuned, responded to slower motion, and had a different molecular profile.

Behavioral/Cognitive

Amygdalostriatal Projections Aid Associative Learning

Laura H. Corbit, Beatrice K. Leung, and Bernard W. Balleine

(see pages 17682–17690)

The posterior dorsomedial striatum (pDMS) is involved both in learning that a given action will produce a particular reward and in subsequently performing the action to obtain the reward. The basolateral amygdala (BLA), which helps motivate goal-directed actions, projects to the pDMS, and Corbit et al. demonstrate that these projections are required both for learning response–outcome associations and for responding appropriately after one outcome is devalued. Rats learned to press levers to receive different rewards and continued to press the levers when the associated rewards were reversed. After one reward was devalued, intact rats pressed the lever most recently associated with that reward less often. But if BLA–pDMS connections were disrupted before lever–reward associations were reversed, rats pressed the lever initially associated with the devalued reward less often, suggesting they failed to learn the new action–outcome association. Furthermore, if BLA–pDMS connections were disrupted immediately before testing, rats appeared not to use previously learned associations to direct their actions.

Neurobiology of Disease

Altered Modulation of Glycine Receptors Causes Hyperekplexia

Ning Zhou, Chen-Hung Wang, Shu Zhang, and Dong Chuan Wu

(see pages 17675–17681)

Deficits in glycine-mediated inhibitory signaling cause excessive muscle tone and exaggerated startle responses, a disorder called hyperekplexia. Inherited hyperekplexia is almost always caused by mutations in glra1 that alter surface expression, agonist binding, or channel properties of glycine receptors (GlyRs) containing the α1 subunit. Zhou et al. have found another way glra1 mutations can produce hyperekplexia. The W170S mutation found in some people with hyperekplexia causes the disorder by disrupting zinc-mediated allosteric modulation of GlyR channels. GlyR currents are normally potentiated by low zinc concentrations and inhibited at high zinc concentrations. But the W170S mutation, which is located near the zinc binding site, greatly reduced zinc-mediated potentiation and consequently enhanced zinc-mediated inhibition of α1-subunit-containing GlyRs in HEK cells and cultured neurons. Although agonist sensitivity was reduced in homomeric mutant α1 GlyRs, sensitivity was unaffected in heteromeric α1ß GlyRs, which are most prevalent in the CNS. Furthermore, the mutation did not affect maximal currents or current-voltage relationships in heteromeric channels.