 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, June 11, 2008, 28(24)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Behavioral Effects of Neuroligin Overexpression
Rochelle M. Hines, Longjun Wu, Dustin J. Hines, Hendrik Steenland, Souraya Mansour, Regina Dahlhaus, Roshni R. Singaraja, Xiaoyan Cao, Esther Sammler, Sheriar G. Hormuzdi, Min Zhuo, and Alaa El-Husseini
(see pages 6055–6067)
Neuroligins are cell-adhesion molecules that are enriched at excitatory or inhibitory synapses and can induce presynaptic specializations. Mutations in neuroligins and neurexins, their presynaptic binding partners, are found in families with autism. Hypothesizing that neuroligin levels affect the ratio of excitatory to inhibitory synapses, Hines et al. have overexpressed neuroligin 2 (which is enriched at inhibitory synapses) in the developing mouse brain. As predicted, overexpression increased the size of symmetric (presumably inhibitory) synapses in the frontal cortex and increased the frequency (but not the amplitude) of miniature IPSCs. In addition, mutant mice exhibited frequent limb clasping (a behavior also evident in mouse models of Rett syndrome), postural abnormalities, enhanced startle responses, and early death. Behaviors thought to reflect anxiety, such as preference for the sides of an open arena, were also apparent. Interestingly, the mutant mice, like autistic humans, avoided social interactions, spending less time interacting with novel mice than did controls.
View larger version (73K):
[in this window]
[in a new window]
The paths of wild-type mice (left) and mice overexpressing neuroligin 2 (right) show that the latter spend more time near the walls of an open arena, a sign of increased anxiety. See the article by Hines et al. for details.
Development/Plasticity/Repair
Regulators of Axon Pruning
Eric D. Hoopfer, Andrea Penton, Ryan J. Watts, and Liqun Luo
(see pages 6092–6103)
During metamorphosis, the nervous system is extensively remodeled via pruning and regrowth of axons and dendrites. To explore the molecular mechanisms responsible for one such transformation—pruning of larval axon branches in Drosophila mushroom body
neurons—Hoopfer et al. compared gene expression patterns in neurons isolated before and after the ecdysone pulse that triggers the pruning. They identified 1000 genes that were regulated by ecdysone. Unsurprisingly, many of the regulated genes are involved in cytoskeletal dynamics and proteasomal degradation, and many are transcriptional regulators. Interestingly, genes involved in neurotransmission were differentially regulated by ecdysone. For example, NMDA and serotonin receptors were upregulated, whereas GABA and dopamine receptors were downregulated, suggesting that
Behavioral/Systems/Cognitive
Memory Enhancement by Inducible cAMP Elevation
Carolina Isiegas, Conor McDonough, Ted Huang, Robbert Havekes, Sara Fabian, Long-Jun Wu, Hui Xu, Ming-Gao Zhao, Jae-Ick Kim, Yong-Seok Lee, Hye-Ryeon Lee, Hyoung-Gon Ko, Nuribalhae Lee, Sun-Lim Choi, Jeong-Sik Lee, Hyeon Son, Min Zhuo, Bong-Kiun Kaang, and Ted Abel
(see pages 6220–6230)
The most compelling evidence to date that increasing neuronal cAMP levels enhances learning is provided in this issue by Isegas et al. The authors created a transgenic mouse in which an invertebrate octopamine receptor is expressed specifically in forebrain neurons. Application of octopamine rapidly and transiently increased cAMP in these neurons, leading to increased phosphorylation of a downstream effector, cAMP response element binding protein. Application of octopamine to hippocampal slices from transgenic animals increased the size and duration of long-term potentiation elicited by a single stimulus relative to controls. Intraperitoneal injection of octopamine enhanced contextual fear conditioning induced by foot shock in transgenic mice. By varying the time of octopamine injection (before, immediately after, or 3 h after training, or 30 min before testing), the authors found evidence that elevated cAMP enhanced acquisition, late consolidation, and retrieval of aversive memory. They also found that octopamine enhanced memory for novel object recognition.
Neurobiology of Disease
Mcl-1, a Key Survival Factor
Nicole Arbour, Jacqueline L. Vanderluit, J. Nicole Le Grand, Arezu Jahani-Asl, Vladimir A. Ruzhynsky, Eric C. C. Cheung, Melissa A. Kelly, Alexander E. MacKenzie, David S. Park, Joseph T. Opferman, and Ruth S. Slack
(see pages 6068–6078)
An interplay between proliferation and apoptosis during development determines the number of neurons in the mature brain. Arbour et al. report that Mcl-1 is a key regulator of this interplay, promoting survival of neural progenitors and immature neurons. The authors developed conditional mutant mice in which Mcl-1 is excised only in the developing forebrain. The telencephalon was much smaller in knock-out mice, and the cortical plate was drastically reduced. This was not due to reduced precursor proliferation, but rather to massive apoptosis of neuronal precursors, newly committed cells, and newly migrating neurons. Knock-out of Mcl-1 in cultured mature neurons did not induce apoptosis, but it made neurons more susceptible to apoptosis when exposed to DNA-damaging chemicals. Mcl-1 was rapidly degraded after toxic insult, and maintaining the levels via viral expression enhanced neuronal survival. Mcl-1 is therefore the first Bcl-2 family member found to be individually critical for neuronal survival.
Related articles in J. Neurosci.:
- Synaptic Imbalance, Stereotypies, and Impaired Social Interactions in Mice with Altered Neuroligin 2 Expression
- Rochelle M. Hines, Longjun Wu, Dustin J. Hines, Hendrik Steenland, Souraya Mansour, Regina Dahlhaus, Roshni R. Singaraja, Xiaoyan Cao, Esther Sammler, Sheriar G. Hormuzdi, Min Zhuo, and Alaa El-Husseini
J. Neurosci. 2008 28: 6055-6067.[Abstract] [Full Text] - Mcl-1 Is a Key Regulator of Apoptosis during CNS Development and after DNA Damage
- Nicole Arbour, Jacqueline L. Vanderluit, J. Nicole Le Grand, Arezu Jahani-Asl, Vladimir A. Ruzhynsky, Eric C. C. Cheung, Melissa A. Kelly, Alexander E. MacKenzie, David S. Park, Joseph T. Opferman, and Ruth S. Slack
J. Neurosci. 2008 28: 6068-6078.[Abstract] [Full Text] - Genomic Analysis of Drosophila Neuronal Remodeling: A Role for the RNA-Binding Protein Boule as a Negative Regulator of Axon Pruning
- Eric D. Hoopfer, Andrea Penton, Ryan J. Watts, and Liqun Luo
J. Neurosci. 2008 28: 6092-6103.[Abstract] [Full Text] - A Novel Conditional Genetic System Reveals That Increasing Neuronal cAMP Enhances Memory and Retrieval
- Carolina Isiegas, Conor McDonough, Ted Huang, Robbert Havekes, Sara Fabian, Long-Jun Wu, Hui Xu, Ming-Gao Zhao, Jae-Ick Kim, Yong-Seok Lee, Hye-Ryeon Lee, Hyoung-Gon Ko, Nuribalhae Lee, Sun-Lim Choi, Jeong-Sik Lee, Hyeon Son, Min Zhuo, Bong-Kiun Kaang, and Ted Abel
J. Neurosci. 2008 28: 6220-6230.[Abstract] [Full Text]
This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Alert me to new issues of the journal Download to citation manager 
Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content
|
|
|
|
 |
|