Cellular/Molecular
Hair Cells Lacking Tip Links Respond to Mechanical Stimuli
Walter Marcotti, Laura F. Corns, Terri Desmonds, Nerissa K. Kirkwood, Guy P. Richardson, et al.
(see pages 5505–5514)
The stereocilia on auditory hair cells are arranged by height. Sound-induced vibration of the basilar membrane deflects the stereocilia in the direction of the tallest, exerting a force on tip links that connect the top of each stereocilium to adjacent taller stereocilia. This force causes mechanosensitive ion channels near the tip links to open. Accumulating evidence suggest that tip-link-associated channels are not the only mechano-electrical transducer (MET) channels in hair cells, however. Marcotti et al. found that strong mechanical stimuli could still elicit currents in mouse hair cells after tip links between stereocilia were severed with a calcium chelator. In contrast to normal MET currents, these currents usually occurred during the negative phase of a sine wave stimulus, suggesting they occurred when stereocilia were deflected away from the tallest in the bundle. Similar currents were detected in hair cells after tip links were eliminated by overstimulation or genetic mutation, as well as in immature hair cells that had not yet formed tip links.
Development/Plasticity/Repair
Tbr2 Specifies Some Non-Image-Forming Ganglion Cells
Neal T. Sweeney, Hannah Tierney, and David A. Feldheim
(see pages 5447–5453)
Researchers have identified >20 types of retinal ganglion cells (RGCs) that process different types of visual information. Although most RGCs contribute to generating images of the external world, several types do not send signals to image-forming brain areas. Instead, these RGCs project to areas involved in functions like adapting to ambient light, stabilizing retinal images, and regulating circadian rhythms. Like all cells, RGCs acquire their unique functions through the expression of cell-type-specific transcription factors. Sweeney et al. report that the transcription factor Tbr2 is required for specification of many non-image-forming RGCs. Tbr2 was expressed in ∼10% of RGCs in the retinas of young mice. Several molecularly distinct RGC types expressed Tbr2; nearly all of these were previously shown to project to non-image-forming brain areas. Furthermore, Tbr2-labeled projections were largely restricted to brain areas involved in non-image-forming functions. Knocking out Tbr2 in RGCs reduced projections to these areas and diminished the pupillary light reflex, showing that Tbr2 contributes to the development of this pathway.
Systems/Circuits
Netrin Directs Formation of Some Electrical Synapses in Flies
Brian O. Orr, Melissa A. Borgen, Phyllis M. Caruccio, and Rodney K. Murphey
(see pages 5416–5430)
Interaction between Netrin and its receptor, Frazzled, has roles at multiple stages of nervous system development, including migration, axon guidance, and synapse formation. Identifying all its roles is therefore difficult. To examine roles of Netrin–Frazzled signaling in the development of giant fiber (GF) synapses in Drosophila, Orr et al. resorted to examining a small percentage of Netrin-deficient animals that survived beyond the larval stage. In most of these flies, the electrical-chemical synapse between the GF and motor neuron TTMn was abnormal. In some cases, the TTMn dendrite on which the GF synapse normally forms did not grow, and in others the GF axon failed to terminate in the proper region. But even when the GF terminated appropriately on the TTMn dendrite, electrical transmission was impaired because expression of the gap junction protein Innexin was diminished in the presynaptic terminal. Interestingly, however, gap junctions between the GF and nearby PSI motor neurons were unaffected. Thus, Netrin–Frazzled signaling has wide-ranging, but cell-type-specific roles.
Neurobiology of Disease
Heroin Reduces Glutamate Uptake in Nucleus Accumbens
Hao-wei Shen, Michael D. Scofield, Heather Boger, Megan Hensley, and Peter W. Kalivas
(see pages 5649–5657)
Addictive drugs enhance dopaminergic signaling in the nucleus accumbens (NAc) and prefrontal cortex, which promotes reward learning. This learning causes people to seek more drug and impairs their ability to inhibit drug seeking. With repeated drug use, cues associated with drug use can lead to relapse even in long-abstinent people. The molecular mechanisms underlying these effects include increased glutamatergic signaling in the NAc, which appears to occur partly as a result of reduced glutamate clearance by the glial excitatory amino acid transporter GLT-1. Shen et al. found that surface expression of GLT-1 and uptake of glutamate were reduced in the core region of NAc in rats that had self-administered heroin for 14 days and then abstained for 14 days. The decay time of EPSCs mediated by NMDA receptors was prolonged in NAc from these animals, suggesting spillover of glutamate to extrasynaptic receptors was greater than normal. Restoring GLT-1 function reduced synaptic spillover, and more importantly, reduced cue-induced drug seeking.