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The Journal of Neuroscience, June 24, 2009, 29(25)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Complexin Knock-Out Reduces Release Probability in Auditory Neurons
Nicola Strenzke, Soham Chanda, Cornelia Kopp-Scheinpflug, Darina Khimich, Kerstin Reim, Anna V. Bulankina, Andreas Neef, Fred Wolf, Nils Brose, Matthew A. Xu-Friedman, and Tobias Moser
(see pages 7991–8004)
Complexins are hypothesized to clamp synaptic vesicles in a readily releasable state at the plasma membrane until increases in calcium trigger rapid, synchronous release. Strenzke et al. report that knock-out of complexin I impaired hearing in mice. In normal mice, complexin I was present in the synaptic terminals of spiral ganglion neurons (SGNs) in the cochlear nucleus. Knock-out of complexin appeared to reduce release probability at these synapses: miniature EPSC frequency was reduced, paired-pulse depression was absent, spike latency was reduced, and spike timing was more variable. Evoked EPSCs were smaller in cochlear nucleus neurons of knock-outs, and the probability of spiking was reduced at the onset of SGN stimulation. Additionally, asynchronous release was increased, allowing spiking to continue after SGN stimulation ended. These data support the hypothesis that complexins enable precisely timed, reliable spiking, which is required for accurate representation of auditory inputs.
Development/Plasticity/Repair
GABA-Mediated Excitation and CREB Promote Neuron Survival
Ravi Jagasia, Kathrin Steib, Elisabeth Englberger, Sabine Herold, Theresa Faus-Kessler, Michael Saxe, Fred H. Gage, Hongjun Song, and D. Chichung Lie
(see pages 7966–7977)
Adult neurogenesis contributes to learning and memory, and defects are linked to depression in humans. In rodents, most adult-born neurons die, but increased hippocampal activity can increase survival. GABA-mediated excitation promotes survival of adult-born neurons, and Jagasia et al. report that phosphorylation of the cAMP response element-binding protein (CREB) peaks during the developmental stage when GABA is excitatory. To investigate CREB’s role in neuron survival, the authors inhibited CREB activity in a subset of adult-born neurons by injecting retroviruses encoding ACREB, a polypeptide that prevents DNA binding by CREB. ACREB reduced neuronal survival and caused abnormal dendritic development. Knocking down the Na+–K+–Cl– cotransporter to make GABA inhibitory in newborn neurons reduced CREB phosphorylation and replicated the effects of ACREB. The effects of knockdown were rescued by coexpressing a highly active CREB mutant, suggesting that GABA-mediated excitation activates CREB to promote survival of adult-born neurons.
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Adult-born neurons were transduced with viruses containing red fluorescent protein and either green fluorescent protein (GFP; left) or ACREB GFP (right). Neurons expressing ACREB GFP did not survive. See the article by Jagasia et al. for details.
Behavioral/Systems/Cognitive
Period 3 Genotype Affects Brain Activation After Sleep Loss
Gilles Vandewalle, Simon N. Archer, Catherine Wuillaume, Evelyne Balteau, Christian Degueldre, André Luxen, Pierre Maquet, and Derk-Jan Dijk
(see pages 7948–7956)
Sleep deprivation impairs memory, attention, and decision making. Functional magnetic resonance imaging (fMRI) has provided clues about the neural mechanisms responsible for this impairment, but the results can be difficult to interpret because people vary in their response to sleep deprivation. Some of this variability results from differences in the circadian clock gene Period 3 (Per3): individuals homozygous for five repeats of a particular sequence (genotype Per35/5) are more impaired after sleep deprivation than those with four repeats (Per34/4). Vandewalle et al. used fMRI to examine the neural underpinnings of this difference. Subjects performed a memory task in the morning and evening, before and after sleep deprivation. Although the task was kept short to eliminate differences in performance, cortical activation was reduced in Per35/5 subjects in the evening of a normal day and further reduced after sleep deprivation. In contrast, cortical activation was maintained in Per34/4 individuals, and additional areas were activated after sleep deprivation, suggesting recruitment of these areas may help maintain cognitive function.
Neurobiology of Disease
Aβ Immunization Decreases Abnormal Tau Phosphorylation
Donna M. Wilcock, Nastaran Gharkholonarehe, William E. Van Nostrand, Judianne Davis, Michael P. Vitek, and Carol A. Colton
(see pages 7957–7965)
It is not clear whether neurodegeneration and cognitive decline in Alzheimer’s disease (AD) depend more on β-amyloid (Aβ) deposition in plaques or on accumulation of abnormally phosphorylated tau in neurofibrillary tangles, but a prominent hypothesis driving therapy development posits that Aβ aggregation is the primary event that leads to other pathologies. Immunization against Aβ is a promising treatment that reduces Aβ deposition and improves cognitive performance, but its effect on tau hyperphosphorylation and neuronal death have not been tested because no mouse model exhibiting all three AD-associated pathologies has been available. Using two recently developed transgenic mouse lines, Wilcock et al. now demonstrate that immunization against Aβ does indeed reduce tau pathology and neuron loss, as well as improving performance on a memory task. Unfortunately, immunization also induced vascular microhemorrhaging, which might limit the usefulness of immunotherapy for treatment of AD.
Related articles in J. Neurosci.:
- Functional Magnetic Resonance Imaging-Assessed Brain Responses during an Executive Task Depend on Interaction of Sleep Homeostasis, Circadian Phase, and PER3 Genotype
- Gilles Vandewalle, Simon N. Archer, Catherine Wuillaume, Evelyne Balteau, Christian Degueldre, André Luxen, Pierre Maquet, and Derk-Jan Dijk
J. Neurosci. 2009 29: 7948-7956.[Abstract] [Full Text] - Amyloid Reduction by Amyloid-β Vaccination Also Reduces Mouse Tau Pathology and Protects from Neuron Loss in Two Mouse Models of Alzheimer's Disease
- Donna M. Wilcock, Nastaran Gharkholonarehe, William E. Van Nostrand, Judianne Davis, Michael P. Vitek, and Carol A. Colton
J. Neurosci. 2009 29: 7957-7965.[Abstract] [Full Text] - GABA-cAMP Response Element-Binding Protein Signaling Regulates Maturation and Survival of Newly Generated Neurons in the Adult Hippocampus
- Ravi Jagasia, Kathrin Steib, Elisabeth Englberger, Sabine Herold, Theresa Faus-Kessler, Michael Saxe, Fred H. Gage, Hongjun Song, and D. Chichung Lie
J. Neurosci. 2009 29: 7966-7977.[Abstract] [Full Text] - Complexin-I Is Required for High-Fidelity Transmission at the Endbulb of Held Auditory Synapse
- Nicola Strenzke, Soham Chanda, Cornelia Kopp-Scheinpflug, Darina Khimich, Kerstin Reim, Anna V. Bulankina, Andreas Neef, Fred Wolf, Nils Brose, Matthew A. Xu-Friedman, and Tobias Moser
J. Neurosci. 2009 29: 7991-8004.[Abstract] [Full Text]
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