Estimating the Readily Releasable Pool
Krista L. Moulder and Steven Mennerick
(see pages 3842-3850)
The readily releasable pool (RRP) is a catchy name for the functionally defined subset of synaptic vesicles that are on-call for release. However, whether they are “ready” appears to depend on how and where they receive the call to action. In this week's Journal, Moulder and Mennerick report that for synapses at cultured excitatory neurons, sucrose application mobilized an RRP that was five times larger than that released by 20 Hz trains of action potentials. The authors ruled out receptor saturation or desensitization as major causes of the discrepancy. Rather, the discrepancy appeared to be attributable to so-called reluctant vesicles that could be coaxed into action with higher external calcium during action potential trains or with potassium-evoked depolarization. However, in GABAergic neurons, hypertonic sucrose application and action potential trains yielded similar RRP estimates. The authors interpret their results as suggesting a more heterogeneous population of vesicles in excitatory neurons compared with inhibitory neurons.
RPTPs and Vertebrate Axon Growth
Laurie Stepanek, Andrew W. Stoker, Esther Stoeckli, and John L. Bixby
(see pages 3813-3823)
Receptor protein tyrosine phosphatases (RPTPs) are important in axon guidance during development in Drosophila. These molecules have complex signaling capability, because they can act as ligands or receptors and target an as-yet-poorly-defined set of substrates. This week, Stepanek et al. combined double-stranded RNA interference with in ovo electroporation to examine RPTPs in chick hindlimb nerves. Limb axons first segregate at the base of the limb into dorsal and ventral groups and then diverge in the limb toward target muscles. The authors unilaterally targeted protein tyrosine phosphatase (PTP)-δ, PTP-σ, or PTP receptor type O (PTPRO), all of which are expressed in chick motor neurons during development. They estimated that targeted RPTPs were reduced by >50%. Knock-down of each RPTP particularly affected a dorsal nerve, the anterior iliotibialis (AITIB). The AITIB was smaller, had abnormal fasciculation, or was absent. PTPRO caused the most striking phenotype. However, reduced expression of multiple RPTPs produced less-severe phenotypes, suggesting a competitive interaction between RPTPs.
Bigger and Better Receptive Fields through Sharing
Karl Farrow, Alexander Borst, and Juergen Haag
(see pages 3985-3993)
In the blowfly, vertical system (VS) tangential cells detect downward motions in the visual field. The dendritic fields of these 10 specialized cells (VS1-VS10) are distributed like soldiers with arms extended from lateral to medal across the lobula plate in the blowfly's optic lobe. If the receptive field of VS cells depended solely on retinotopic projection to their dendrites, each would detect movement in ∼30-40° of the visual field, but they can respond to motion well beyond this limit. VS cells are also connected in series by electrical junctions, as reported previously. This week, Farrow et al. photoablated individual VS cells to ascertain how these lateral connections affect their functional properties. Receptive fields were diminished by ablation of closely neighboring upstream, but not downstream, cells. Thus organization of VS cells in a functional chain, rather than in a syncytium of recurrent reciprocal connections, can explain their exceptionally broad receptive fields.
Neurobiology of Disease
Managing Cellular Stress in Worm Dopamine Neurons
Songsong Cao, Christopher C. Gelwix, Kim A. Caldwell, and Guy A. Caldwell
(see pages 3801-3812)
Dopamine neurons appear to be particularly sensitive to cellular stress caused by protein misfolding or oxidative damage. For example, mutant or overexpressed α-synuclein causes intracellular inclusions (Lewy bodies) and cell degeneration of dopamine neurons. Such mechanisms are considered central to the pathogenesis of Parkinson's disease. Chaperone proteins can protect against cell stress and oxidative damage by enhancing degradation of ubiquinated proteins. This week, Cao et al. tested the protective ability of the chaperone protein torsinA in dopaminergic (DA) neurons of Caenorhabditis elegans. Mutations in torsinA underlie the hereditary movement disorder known as early-onset torsion dystonia. TorsinA is also highly expressed in dopamine neurons, and it associates with α-synuclein in Lewy bodies. The authors treated worms with 6-hydroxydopamine (6-OHDA), selectively targeting the eight DA neurons for degeneration. TorsinA overexpression protected neurons from degeneration induced either by 6-OHDA or by α-synuclein overexpression. For 6-OHDA-induced toxicity, the action of torsinA appears to be linked to reduced surface expression of the dopamine transporter.