A Non-Cell-Autonomous Effect of IP3 Receptors
Chihiro Hisatsune, Yukiko Kuroda, Takumi Akagi, Takashi Torashima, Hirokazu Hirai, Tsutomu Hashikawa, Takafumi Inoue, and Katsuhiko Mikoshiba
(see pages 10916–10924)
The 1,4,5-trisphosphate receptor type 1 (IP3R1) is highly expressed in cerebellar Purkinje cells, with activation leading to release of intracellular calcium. Thus, when Hisatsune found that cultured Purkinje cells from IP3R1 knock-out mice had abnormal dendrites, that might not have been so surprising. The dendrites in mutant mice showed a longer total length, but were less “bushy,” with fewer branches and a thinner primary dendrite. However, the surprise was that the lack of granule cell IP3R1s was responsible for the Purkinje cell defect. The authors revealed this non-cell-autonomous effect by culturing wild-type and mutant Purkinje cells alone or with wild-type and mutant granule or glial cells. The defective morphology in Purkinje cells resulted from a decrease in BDNF expression in mutant granule cells and could be rescued by a 5 d treatment of the cultures with exogenous BDNF. In vivo, the dendritic abnormalities were less dramatic, but still apparent.
Determining Sites of Synapse Formation
Shasta L. Sabo, Raquel A. Gomes, and A. Kimberley McAllister
(see pages 10813–10825)
What determines where synapses will form along an axon? Sabo et al. try to answer this question by distinguishing between two possibilities. Either presynaptic terminals can form anywhere along the axon, or synaptogenesis is restricted to specific sites. To watch the action, the authors used time-lapse imaging in cultured cortical neurons and monitored labeled presynaptic transport vesicles (STVs) as they paused at predefined sites along axons, even in the absence of neuronal or glial contact. Contact with a neuroligin-expressing non-neuronal cell induced formation of presynaptic terminals specifically at STV pause sites. Stable contacts with dendritic filopodia also occurred selectively at STV pause sites. The authors suggest that regulation of STV pausing might be critical for the accumulation of presynaptic proteins at nascent synapses and propose that en passant synapses form specifically at predefined sites in young axons. What molecules “predefine” these sites remains to be determined.
Multitasking in the Leech
Kevin L. Briggman and William B. Kristan Jr
(see pages 10925–10933)
The “no double dipping” rule apparently doesn’t necessarily apply to neuronal circuits. This week, Briggman and Kristan demonstrate that the circuits driving two distinct motions, swimming and crawling in the medicinal leech, involve many of the same neurons. Using a FRET (fluorescence resonance energy transfer)-based voltage-sensitive dye, the author simultaneously recorded from 80% of the 400 or so neurons in segmental ganglion 10 during induced swimming or crawling. Previous studies had indicated that the same neuron can drive more than one behavior, but such studies had primarily recorded from single cells. The authors, by sampling large populations of neurons, found that twice as many neurons oscillate during crawling as during swimming. In addition, 93% of the neurons that oscillated with swimming also oscillated with crawling. Crawling may be more primitive, the authors suggest, and the swim circuit may have evolved by sharing part of the crawl circuit. Swim coaches take note.
Neurobiology of Disease
MeCP2 and Transynaptic BDNF Signaling
Hong Wang, Shyue-an Chan, Michael Ogier, David Hellard, Qifang Wang, Corey Smith, and David M. Katz
(see pages 10911–10915)
Around the first birthday, a toddler with Rett syndrome starts having trouble speaking and walking. Within a few years, the breathing and heart rate become unstable and hand movements abnormal. This severe neurological condition is caused by loss-of-function mutations in the gene for methyl-CpG-binding protein-2 (MeCP2). This week, Wang et al. explored one possible disease mechanism using mice lacking MecP2. Previous work indicated that MecP2 regulates expression of brain-derived neurotrophic factor (BDNF). Now, the authors describe that, with age, BDNF levels in MecP2 null mice decline sharply in neural structures important for respiration and autonomic control, including the nodose ganglia and brainstem. BDNF secretion also declined in these cells, but high-frequency electrical stimulation could rescue normal levels of BDNF release. The latter may be attributable to generalized increase in exocytosis in Mecp2 null mice because chromaffin cells showed an increase in the readily-releasable pool of dense core vesicles and in evoked release.