Cellular/Molecular
Jaw Sensory Afferents Have Unusual Electrical Coupling
Sebastian Curti, Gregory Hoge, James I. Nagy, and Alberto E. Pereda
(see pages 4341–4359)
Mastication is produced by a central pattern generator that is modified to accommodate foods of different textures by sensory neurons that innervate periodontal mechanoreceptors and spindles in jaw-closing muscles. These afferents are unique among primary sensory neurons, because their cell bodies reside within the CNS—in the mesencephalic trigeminal nucleus (MesV)—and receive inputs from other brainstem nuclei. MesV neurons were among the first mammalian CNS neurons proposed to be electrically coupled, but Curti et al. are the first to demonstrate this definitively. Electrical coupling allowed subthreshold depolarization in paired cells to summate and elicit synchronous spiking. The coupling also exhibited several unusual features: most neurons were coupled in pairs, rather than in more extensive networks; electrical coupling first appeared relatively late in development; and only a small fraction of connexin channels were open at a given time. In addition, the coupling strength exhibited voltage-dependent amplification and was optimal at stimulation frequencies near 50 Hz.
Development/Plasticity/Repair
Chondrolectin Is Involved in Axon Pathfinding
Zhen Zhong, Jochen Ohnmacht, Michell M. Reimer, Ingolf Bach, Thomas Becker, et al.
(see pages 4426–4439)
In zebrafish, each spinal hemisegment has three primary motor neurons whose axons grow toward different muscle targets. The axons fasciculate after exiting the spinal cord, and they grow together to the horizontal myoseptum, where they diverge to innervate dorsal, ventral, or intermediate muscles. The expression of guidance receptors that direct different axon trajectories is regulated by LIM homeodomain transcription factors. To identify molecules involved in axon growth, Zhong et al. blocked LIM function selectively in postmitotic motor neurons, and compared the expression profile of these neurons to those in controls. Chodl, which encodes chondrolectin, was one of three genes expressed selectively in motor neurons, and it was upregulated before and during axon outgrowth. After knockdown of chodl, motor neurons grew normally to the horizontal myoseptum, but then stalled, resulting in reduced muscle innervation. Interestingly, chodl mRNA is improperly spliced in mouse models of spinal muscular atrophy, indicating developmental defects might contribute to this disease.
Motor neuron axons grow out of the spinal cord in normal zebrafish (left), but blocking LIM function caused axons to stay within the spinal cord (right). See the article by Zhong et al. for details.
Behavioral/Systems/Cognitive
Glutamate Transporter Hyperpolarizes Rod Bipolar Cells
Tomomi Ichinose and Peter D. Lukasiewicz
(see pages 4360–4371)
Light leads to depolarization of rod bipolar cells (RBCs), causing them to release glutamate, which activates receptors on AII amacrine cells. Glutamate also binds to excitatory amino acid transporter (EAAT) 5 on RBC presynaptic terminals, thus producing a large glutamate-activated Cl− conductance that hyperpolarizes RBCs. RBC terminals are also hyperpolarized by glycinergic and GABAergic feedback from different types of amacrine cells. Ichinose and Lukasiewicz show that these two types of inhibition—that mediated by glycine or GABA receptors and that mediated by EAAT5—function at different light intensities in mice. Receptor-mediated inhibition predominated in dim light and was attenuated in bright light, whereas EAAT5-mediated hyperpolarization occurred only in bright light. EAAT5-mediated inhibition was elicited by glutamate released by RBCs and it reduced light-induced EPSPs, thus reducing vesicle release. Together, these two inhibitory processes extend the dynamic range of RBC inhibition. EAAT5-mediated inhibition might also help to attenuate the rod pathway as light intensity increases.
Neurobiology of Disease
Resting Activity Is Correlated with Amyloid Deposits in Mice
Adam W. Bero, Adam Q. Bauer, Floy R. Stewart, Brian R. White, John R. Cirrito, et al.
(see pages 4334–4340)
When people are not actively engaged with their surroundings, for example, when reminiscing or imagining future events, the blood oxygen level-dependent signal measured by functional imaging increases in several brain regions that are collectively called the default mode network. This network includes medial prefrontal cortex, posterior cingulate cortex, retrosplenial cortex, and the hippocampus. Interestingly, many of these regions show reduced glucose metabolism, atrophy, and deposition of amyloid plaques in Alzheimer's disease (AD). It has therefore been hypothesized that regions active during rest are most susceptible to amyloid pathology. Bero et al. report that similar relationships occur in mice. Bilateral correlated activity was reduced in frontal, motor, cingulate, and retrosplenial cortex of old mice that expressed an AD-associated mutant protein compared to young transgenic mice. The regions with the greatest decrease in correlated activity had the greatest density of amyloid plaques. Moreover, plaque density in a given region was correlated with the bilateral correlation strength in younger mice.
