This week, Huang et al. report on avtemperature-sensitive (TS) Drosophila mutant with a catchy name, rolling blackout (rbo). Why rolling blackout? Well, it seems that this putative transmembrane lipase is required for phototransduction in Drosophila. However, rbo TS mutants become reversibly paralyzed above 37¡ãC, suggesting an additional role in neurotransmission. RBO protein was expressed in synaptic boutons, and TS mutants showed a rapid and reversible block of central and peripheral synaptic transmission. In electron micrographs, the neuromuscular junction (NMJ) of rbo mutants appeared normal, but after 10 minutes at 37¡ãC, synaptic vesicle number had nearly tripled, most compatible with a block of exocytosis at a postdocking step, possibly priming or fusion. There was a synergistic genetic interaction between rbo and syntaxin1A but not with proteins affecting presynaptic calcium influx, SNARE complex disassembly, or vesicle recycling. The authors propose that RBO may regulate the levels of fusogenic lipids such as diacyglycerol or phosphatidylinositides.
2. Handling Stress
Kristina A. Fenoglio, Yuncai Chen, and Tallie Z. Baram
Human handling of rat pups induces lifelong changes in their response to stress, a remarkable example of experience-dependent neuroplasticity. It turns out that it is not the handling per se but the postseparation maternal licking and grooming that leads to reduced expression of corticotropin releasing hormone (CRH), a lowered hormonal stress response, and upregulated hippocampal glucocorticoid receptors. This week, Fenoglio et al. investigated the mechanisms underlying CRH reduction. CRH mRNA was reduced in the hypothalamic paraventricular nucleus of pups handled daily between P2 and P8 but not of those handled just once. c-fos was expressed in so-called neural stress integrators, the thalamic paraventricular nucleus (PVT), central amygdala (ACe), and bed nucleus of stria terminalis (BnST). A single handling event triggered c-fos expression in ACe and BnST, but recurring handling was required in PVT. Daily handling also reduced phosphorylated cAMP response element-binding protein and extracellular-signal regulated kinase that are key regulators of CRH gene transcription in the hypothalamus.
3. From Maternal to Hunting Behavior in the Periaqueductal Gray
M. H. Sukikara, S. R. Mota-Ortiz, M. V. Baldo, L. F. Fel¨ªcio, and N. S. Canteras
Nursing rat dams sensitized to morphine abandon their maternal duties when given another low dose, preferring a quite different activity, predatory hunting. Sukikara et al. looked to the periaqueductal grey (PAG) as the seat of a peculiar behavioral switch. The authors returned the pups to their cage after a 1 h absence during which the dams were injected with morphine. Saline-injected rats and those that underwent NMDA lesions in the rostral lateral PAG immediately retrieved, grouped, groomed, and nursed their pups. Morphine inhibited maternal behaviors in dams that were intact or had lesions to other PAG regions. The morphine-treated dams also displayed a greater propensity for predatory hunting. When given the choice between caring for pups and hunting cockroaches, only those with lateral PAG lesions displayed maternal behaviors. The authors propose that the lateral PAG is important in adaptive changes in behavior.
4. Febrile Seizures and GABAA Receptor Trafficking
Jing-Qiong Kang, Wangzhen Shen, and Robert L. Macdonald
Febrile seizures are a common, often benign, early childhood occurrence. Recent studies have identified several ion channel mutations in families with febrile seizures. One of these involves mutations in the ¦Ã2 subunit of the GABAA receptor. Kang et al. investigated the function of mutant ¦Ã2 subunits coexpressed with ¦Á1 and ¦Â2 subunits in heterologous cells. They examined three ¦Ã2 mutations implicated in febrile seizures (R43Q, K289M, and Q351X) and a mutation not associated with febrile seizures (¦Á1 A322D). Because ¦Ã2 subunits affect receptor trafficking, clustering, and synaptic maintenance, the authors tested the hypothesis that these mutations might alter receptor trafficking in a temperature-dependent manner. Surface expression of receptors containing mutant ¦Ã2 subunits was significantly reduced at 40¡ãC compared with 37¡ãC. Cultured hippocampal neurons expressing mutant ¦Ã2 subunits also had decreased surface expression and GABA-induced currents at 40¡ãC. The results suggest one possible mechanism for febrile seizures in patients with these mutations.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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