This Week in the Journal
Mossy Fiber LTD: You Can Have it Both Ways
Saobo Lei and Chris J. McBain
(see pages 2112-2121)
Synaptic plasticity takes many molecular forms. In this week's Journal, Lei and McBain explore two types of long-term depression (LTD) at CA3 inhibitory synapses between mossy fibers and stratum lucidum interneurons. Both types require influx of postsynaptic calcium, but whereas calcium-permeable AMPA-type glutamate receptors (CP-AMPARs), when present, are sufficient to induce LTD at some of these synapses, NMDA receptors (NMDARs) are required for LTD at synapses expressing calcium-impermeable (CI)-AMPARs. The authors used a three-pronged approach to determine the site of LTD expression in each case. They measured whether the two forms of LTD altered neurotransmitter release probability, the level of released glutamate fluctuations in the cleft, and/or AMPA receptor trafficking in the postsynaptic membrane. LTD expression appeared to be presynaptic at synapses with CP-AMPARs, whereas postsynaptic mechanisms, possibly calcium-evoked AMPAR endocytosis, mediated LTD evoked by CI-AMPARs and NMDARs. The parallel LTD mechanisms give a familiar answer to the question "presynaptic or postsynaptic?" It depends.
The March of the reelin-Positive Cells
Keiko Takiguchi-Hayashi, Mariko Sekiguchi, Shizuko Ashigaki, Masako Takamatsu, Hiroshi Hasegwawa, Rika Suzuki-Migishima, Minesuke Yokoyama, Shigetada Nakanishi, and Yasuto Tanabe
(see pages 2286-2295)
The neocortex is organized into discrete laminar and cortical areas with the help of neurons that express reelin, an extracellular protein that governs neuronal migration. This insight was initially provided by two accidents of nature, the reeler mouse and human congenital lissencephaly, a severe migration disorder resulting in a smooth cortical surface that lacks sulci. Reelin-positive cells reside in the marginal zone (MZ), an area derived from the early cortical plate. However the temporal and spatial origin of these neurons is still in question. This week, Takiguchi-Hayashi et al. use cell-labeling techniques to trace reelin-positive cells back to the time and place from which they arose. They found that reelin-positive cells originate in the caudomedial wall of telencephalic vesicles and then migrate to the MZ, forming a caudomedial-to-rostrolateral gradient. Thus reelin-positive cells are generated extrinsic to the neocortex in an area aptly named the cortical "hem."
Active Head Motion and the Vestibular Nuclei
Jefferson E. Roy and Kathleen E. Cullen
(see pages 2102-2111)
How can we distinguish between our own self-generated movements and those of the external world? This ability to differentiate between so-called "reafference" and "exafference" is something most of us take for granted. Over 50 years ago, Von Holst and Mittelstaedt hypothesized that the brain generates a sensory expectation based on motor output, compares it with actual sensation, and subtracts the self-generated sensation, creating a perception of the outside world. This week, Roy and Cullen provide evidence for such comparison and cancellation during early vestibular processing. They recorded from "vestibular-only" neurons of the vestibular nucleus while monkeys made head movements. These cells are known to receive direct vestibular afferent input but respond much better to passive movements than to self-generated head movements. A cancellation signal was generated only when the activation of neck proprioceptors matched the motor-generated expectation. Thus this mechanism acts to eliminate self-movements from the subsequent computation of orientation and posture control.
Neurobiology of Disease
Spinal Cord Bypass Surgery
Lucas Campos, Zhuo Meng, Guoli Hu, David T. W. Chiu, Richard T. Ambron, and John H. Martin
(see pages 2090-2101)
Despite some successes, therapeutic repair of spinal cord injury has eluded us. Now Campos et al. explore an alternate route between brain and body: around, rather than through, an injury. After cutting the T13 motor nerve in rats, they inserted the distal nerve stump to the lumbosacral spinal cord, where it resprouted and grew into gray and white matter. The growth holds functional promise: after spinal cord hemisection at L2/3, the T13 nerve "bridge" facilitated muscle contraction and lessened spasticity and wasting. Because the new circuitry is not impeded by scar formation, the therapeutic strategy may work for chronic as well as acute spinal injury. The motor neurons made functional connections with novel targets: other spinal neurons rather than muscle cells. Presumably it would take extensive training to volitionally control these rerouted motor neurons that normally control abdominal muscles, but there seems reason to be hopeful.