Irina Dudanova, Simon Sedej, Mohiuddin Ahmad, Henriette Masius, Vardanush Sargsyan, Weiqi Zhang, Dietmar Riedel, Frank Angenstein, Detlev Schild, Marjan Rupnik, and Markus Missler
The secretory function of neurons and neuroendocrine cells share many characteristics, as exemplified by work this week by Dudanova et al. The authors previously showed that a-neurexins are required for the efficient synaptic release of neurotransmitter, which was suggested to be attributable to regulation of voltage-dependent calcium channels. Now, they turned their focus to calcium-dependent exocytosis in neuroendocrine cells. Adult mice lacking two of the three a-neurexin genes were hypomorphic with a 40% reduction in body weight. Whole-cell patchclamp measurements of membrane capacitance of melanotrophs in pituitary gland slices indicated that secretion was indeed markedly reduced. The effect was most pronounced in newborn triple knock-outs lacking all three genes. However, calcium currents in melanotrophs were not reduced in the knock-outs, somewhat at odds with previous studies in neurons. The authors rather suggest that a-neurexins affect coupling of calcium channels to the release-ready pool of vesicles and to G-protein-coupled receptors.
Christina von der Ohe, Corinna Darian-Smith, Craig C. Garner, and H. Craig Heller
Each winter, some animals deal with the cold and with limited food supplies by hibernating. This week, von der Ohe et al. look at the remarkable brain plasticity that accompanies this annual ritual in goldenmantled ground squirrels. Hibernating animals go through bouts of torpor, lasting up to 2 weeks, during which body temperature can drop to near freezing and neuronal activity almost stops. Using iontophoretic injections of dye into fixed tissue sections, the authors examined the structure of neurons in the cerebral cortex, hypothalamus, and thalamus of hibernating squirrels at several stages of torpor and at different temperatures. Cell bodies, dendrites, and spines retracted when the animals entered into torpor. Although the extent of retraction depended on the minimum body temperature reached during torpor, the neuronal structures always recovered to their original conformation within just 2 h of returning to normal body temperatures. Whether they remember where they buried their acorns remains to be tested.
Kafui Dzirasa, Sidarta Ribeiro, Rui Costa, Lucas M. Santos, Shih-Chieh Lin, Andres Grosmark, Tatyana D. Sotnikova, Raul R. Gainetdinov, Marc G. Caron, and Miguel A. L. Nicolelis
In Oliver Sack's book "Awakenings," survivors of the 1917–1928 epidemic of encephalitis lethargica temporarily "awaken" from their catatonic state after receiving the then-new drug L-dopa. Although not quite as poetic, Dzirasa et al. tell of another link between dopamine and sleep–wake states. The authors investigated hippocampal local field potentials and electromyographic activity in mice with either genetically or pharmacologically induced changes in dopamine levels. Upon exposure to a novel environment, dopamine transporter–knock-out (DATKO) mice and wild-type mice treated with amphetamine, manipulations resulting in increased extracellular dopamine, exhibited neural activity typical of rapid eye movement (REM) sleep, yet the animals were awake. The D2 receptor antagonist haldol blocked this activity. In contrast, treatment of DAT-KO mice with a tyrosine hydroxylase inhibitor, which completely depleted dopamine stores, abolished REM sleep altogether. These animals exhibited severe Parkinson-like motor symptoms and a novel awake state with oscillations typical of slow-wave sleep.
Yannick Simonin, Yves Charron, Peter Sonderegger, Jean-Dominique Vassalli, and Ann C. Kato
Plasminogen activators (PAs) are perhaps best known in the clinical world as intravascular clot busters. However, these fibrinolytic agents are also expressed in neurons and glia and have been implicated in axon outgrowth, regeneration, and neural injury. This week, Simonin et al. test the role of these serine proteases in axon degeneration in mice with progressive motor neuronopathy ( pmn/pmn). This so-called "dying back" motor neuron disease starts in axon terminals, followed by degeneration of cell bodies, and is paralleled by increases in PA levels in sciatic nerves. The pmn/pmn animals show weakness and muscle atrophy and die by 6 weeks of age. The authors crossed pmn mice with transgenic mice overexpressing neuroserpin, an axonally secreted inhibitor of PA. Surprisingly, the double-mutant mice lived 50% longer than their pmn/pmn counterparts. In addition to decreased PA activity, the double mutants had more myelinated axons and surviving motoneurons in the spinal cord and cranial nuclei.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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