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The Journal of Neuroscience, December 3, 2008, 28(49)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Norepinephrine Is Released from Sour Taste Cells
Yijen A. Huang, Yutaka Maruyama, and Stephen D. Roper
(see pages 13088–13093)
Gustatory coding and processing within taste buds is more complex than once believed, and much remains unknown. Remarkably, most of the known taste receptors proteins—those responding to sweet, bitter, and umami—are expressed on type II "receptor cells" that do not have obvious synaptic release sites. These cells release ATP through gap junction hemichannels. Only type III "presynaptic cells" form traditional synapses, and recently Huang et al. reported that these cells release serotonin in response to acids (sour taste), by a mechanism that might not require transmembrane receptors. To study neurotransmitter release from mouse taste cells, Huang et al. use biosensors—Chinese hamster ovary cells transfected with transmitter receptors and loaded with calcium sensors. Using this technique, they now report that approximately one-third of presynaptic cells release norepinephrine as well as serotonin when stimulated with KCl or acid. Norepinephrine might modulate the responsiveness of gustatory afferents, but its postsynaptic target is not clear.
Development/Plasticity/Repair
Microtubules Invade Dendritic Spines
Xindao Hu, Chris Viesselmann, Sookin Nam, Elliott Merriam, and Erik W. Dent
(see pages 13094–13105)
Actin filaments and microtubules are major determinants of neuronal form. During neurite outgrowth, actin forms the motile periphery of growth cones, and subsequent invasion of microtubules underlies neurite extension. In mature neurons, actin is the primary structural component of dendritic spines, and microtubules are largely restricted to dendritic shafts and axons. Microtubules have rarely been detected in spines, but by using a fluorescent marker of growing microtubules and limiting illumination with total internal reflectance microscopy, Hu et al. provide evidence that microtubules transiently invade dendritic spines in mouse neuronal cultures. Invasions were rare (targeting
9% of spines during an hour) and microtubules persisted for just minutes before depolymerizing, but increasing neuronal activity increased both the frequency and the duration of incursions. The function of microtubule invasion of spines is unknown, but given that microtubules transport proteins along dendritic shafts, it is conceivable that they similarly deliver proteins to spines.
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A microtubule (green) invading a dendritic spine in a cultured hippocampal neuron. The spine'synapse was labeled with synaptophysin (blue), and the cell was filled with red dye to show its morphology. See the article by Hu et al. for details.
Behavioral/Systems/Cognitive
Genotype Influences Placebo Responsiveness
Tomas Furmark, Lieuwe Appel, Susanne Henningsson, Fredrik Åhs, Vanda Faria, Clas Linnman, Anna Pissiota, Örjan Frans, Massimo Bani, Paolo Bettica, Emilio Merlo Pich, Eva Jacobsson, Kurt Wahlstedt, Lars Oreland, Bengt Långström, Elias Eriksson, and Mats Fredrikson
(see pages 13066–13074)
Placebos can have impressive effects, from attenuating or enhancing pain to increasing mobility in Parkinson's disease patients. How otherwise inert substances can induce such effects is an intriguing question, so what was once a control condition has become the subject of many investigations. A subject's expectations about treatment outcome are important in the effectiveness of a placebo, and imaging studies reveal that, in subjects that respond to placebos, the placebo activates many of the same brain regions targeted by the active drug. This week, Furmark et al. report that a subject's genotype may also determine the effectiveness of placebo. Subjects with social anxiety disorder underwent functional neuroimaging while giving a short speech before and after sustained placebo treatment. Placebo responsiveness (i.e., reduced scores on anxiety tests) was correlated with reduced activity in the amygdala. Remarkably, responsiveness also depended on which alleles of two serotonin-related genes the subject had.
Neurobiology of Disease
Hsp27 Protects Neurons from Ischemic Damage
R. Anne Stetler, Guodong Cao, Yanqin Gao, Feng Zhang, Suping Wang Zhongfang Weng, Peter Vosler, Lili Zhang, Armando Signore Steven H. Graham, and Jun Chen
(see pages 13038–13055)
Neuronal insults often initiate signaling cascades that lead to release of cytochrome c from mitochondria and subsequently to apoptotic cell death. At the same time, insults activate neuroprotective processes, such as upregulation of members of the heat shock protein (Hsp) family, including Hsp27. Stetler et al. now report that overexpression of Hsp27 in mice significantly decreased the extent of damage resulting from transient ischemia, and improved subsequent sensorimotor and cognitive function. The authors found that Hsp27 directly bound to the kinase domain of apoptosis signal-regulating kinase (ASK1) and thus prevented the downstream effects of ASK1, including release of apoptotic signals from mitochondria, caspase activation, and cell death. Knockdown of ASK1 also reduced ischemic damage, whereas knockdown of Hsp27 increased damage. Because ASK1 activation is an early step in pro-death pathways initiated by neuronal insult, ASK1 and Hsp27 may be valuable targets for protecting the brain from diverse insults.
Related articles in J. Neurosci.:
- Hsp27 Protects against Ischemic Brain Injury via Attenuation of a Novel Stress-Response Cascade Upstream of Mitochondrial Cell Death Signaling
- R. Anne Stetler, Guodong Cao, Yanqin Gao, Feng Zhang, Suping Wang, Zhongfang Weng, Peter Vosler, Lili Zhang, Armando Signore, Steven H. Graham, and Jun Chen
J. Neurosci. 2008 28: 13038-13055.[Abstract] [Full Text] - A Link between Serotonin-Related Gene Polymorphisms, Amygdala Activity, and Placebo-Induced Relief from Social Anxiety
- Tomas Furmark, Lieuwe Appel, Susanne Henningsson, Fredrik Åhs, Vanda Faria, Clas Linnman, Anna Pissiota, Örjan Frans, Massimo Bani, Paolo Bettica, Emilio Merlo Pich, Eva Jacobsson, Kurt Wahlstedt, Lars Oreland, Bengt Långström, Elias Eriksson, and Mats Fredrikson
J. Neurosci. 2008 28: 13066-13074.[Abstract] [Full Text] - Norepinephrine Is Coreleased with Serotonin in Mouse Taste Buds
- Yijen A. Huang, Yutaka Maruyama, and Stephen D. Roper
J. Neurosci. 2008 28: 13088-13093.[Abstract] [Full Text] - Activity-Dependent Dynamic Microtubule Invasion of Dendritic Spines
- Xindao Hu, Chris Viesselmann, Sookin Nam, Elliott Merriam, and Erik W. Dent
J. Neurosci. 2008 28: 13094-13105.[Abstract] [Full Text]
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