Cellular/Molecular
Visualizing Exocytosis in Receptorless Fish
Optical Measurements of Presynaptic Release in Mutant Zebrafish Lacking Postsynaptic Receptors
Weiyan Li, Fumihito Ono, and Paul Brehm
(see pages 10467-10424)
Both anterograde and retrograde signaling are involved in the maturation of synaptic transmission at the neuromuscular junction (NMJ). One of the obvious candidates for the initiation of retrograde signaling is the postsynaptic receptor itself. In fact, in Xenopus and in several invertebrates, inhibition of postsynaptic receptors prevents the modulation of transmitter release that occurs with muscle contact. In this issue, Li et al. directly examined this question using two strains of paralytic zebrafish, nic-1 and sofa potato, that do not express acetylcholine receptors (AChRs) yet have a normal-appearing NMJ. These mutants, unlike mammalian AChR knock-outs, survive long enough to form intact NMJs. The receptorless mutants naturally do not respond to synaptic ACh. Thus the authors monitored presynaptic release optically by labeling presynaptic vesicles with the fluorescent dye FM1-43. Surprisingly, at 4 days of age when the NMJ is fully functional, there was no difference between wild-type and mutant fish. Although this evidence indicates that postsynaptic receptors are not a prerequisite for apparently normal presynaptic function, it does not exclude more subtle effects of receptor activity or signaling via coreleased substances such as ATP or neuropeptides.
Development/Plasticity/Repair
What Hematopoetic Stem Cells Could and Couldn't Do
Primordial Hematopoietic Stem Cells Generate Microglia But Not Myelin-Forming Cells in a Neural Environment
Sandrine Vitry, Julien Y. Bertrand, Ana Cumano, and Monique Dubois-Dalcq
(see pages 10724-10731)
The regenerative potential of stem cells has stimulated great clinical interest as a means to replace or enhance CNS cell function in neurological disorders. A key issue is the extent to which stem cells derived from non-CNS tissue such as the bone marrow can transdifferentiate into neurons or glia. This week, Vitry et al. compared the capacity of embryonic precursors derived from the striatum with those derived from the aorta-gonads-mesonephros (AGM) area of embryonic mice in the generation of myelin-producing oligodendrocytes. Precursor cells from the AGM area are hematopoietic stem cells (HSCs), but some cultured HSCs also express neural markers such as nestin. The authors grafted HSCs into wild-type mice or into hypomyelinated shiverer mice that do not express myelin basic protein. In both cases, HSCs developed into microglia but not into neurons or oligodendrocytes. Striatal precursors, on the other hand, successfully differentiated into neurons and myelinating oligodendrocytes as expected. These results place some limit on “stem cell plasticity,” at least for the conditions used in these experiments.
After growing for 4 d in hematopoietic conditions, many enhanced green fluorescent protein-positive (EGFP+) AGM-sorted precursors expressed CD45 protein (purple), and some coexpressed neural antigens such as PSA-NCAM staining (red at arrowhead). See the article by Vitry et al. for details.
Behavioral/Systems/Cognitive
Monamines and Distinct Olfactory Memories
Dopamine and Octopamine Differentiate between Aversive and Appetitive Olfactory Memories in Drosophila
Martin Schwaerzel, Maria Monastirioti, Henrike Scholz, Florence Friggi-Grelin, Serge Birman, and Martin Heisenberg
(see pages 10495-10502)
Synaptic plasticity in neural circuits underlies the acquisition, storage, and retrieval necessary for learning and memory. But which synapses must change for the recording of a given experience? And how about the quality of the experience - are rewarding events encoded differently from aversive ones? Schwaerzel et al. approach these questions and define different roles for dopamine and octopamine in olfactory memory in the fly Drosophila melanogaster. They paired an odor as the conditioned stimuli (CSs) with one of two unconditioned stimuli (USs), either electric shock (aversive US) or sugar (appetitive US). As expected, flies tested in a T-maze 100 sec later avoided the odor that had been paired with the shock but showed a preference for the sugar-associated odor. The authors confirmed that both memories depend on cAMP in Kenyon neurons in the mushroom body, and that a single CS can be linked to multiple unconditioned stimuli. Interestingly, flies that did not produce octopamine displayed severely disrupted “sugar memory.” In contrast, flies lacking dopamine specifically lost aversive memories. Memory was restored with inducible expression of the transmitters. The authors surmise that although appetitive and aversive memories form in response to the same odor, their linkage to different modulatory transmitter pathways determines their motivational properties.
