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The Journal of Neuroscience, April 15, 2009, 29(15)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Learning and Aging Affect Afterhyperpolarization Size
Elizabeth A. Matthews, John M. Linardakis, and John F. Disterhoft
(see pages 4750–4755)
Learning involves changes in the intrinsic excitability of neurons as well as changes in synaptic strength. As animals age, some cellular mechanisms of learning become less plastic, leading to cognitive decline. For example, the slow afterhyperpolarization (AHP), which counteracts depolarization and limits excitability after trains of action potentials, is reduced by learning and increased during aging. Because the fast AHP that follows single action potentials is also decreased by learning, Matthews et al. examined whether aging increases this current. They conditioned young and old rats in an eye-blink task, then measured AHPs in hippocampal slices. When learning occurred, it was indistinguishable in young and old animals: reductions in slow and fast AHPs occurred similarly in the two groups. In animals that did not learn, the slow AHP was larger in old than young animals, but the fast AHP was unaffected. Therefore, aging has variable effects on different cellular mechanisms of learning.
Development/Plasticity/Repair
Cortical Axons Contain Many mRNAs
Anne M. Taylor, Nicole C. Berchtold, Victoria M. Perreau, Christina H. Tu, Noo Li Jeon, and Carl W. Cotman
(see pages 4697–4707)
Given the length of axons and the rate of axonal transport, protein synthesis in axons must occur if protein levels are to change rapidly at presynaptic terminals. In fact, mRNAs for several proteins, including ribosomal proteins, have been detected in invertebrate and vertebrate peripheral axons. But because isolating CNS axons from somata and dendrites is difficult and in situ hybridization is relatively insensitive, detection of mRNAs in CNS axons has been hindered. Now Taylor et al. have used a recently developed microfluidic chamber that allows segregation of cortical axons into narrow channels to obtain purely axonal mRNAs. Subsequent microarray analysis identified >300 mRNAs in axons, including cytoskeletal proteins and proteins involved in axon transport. Axotomy altered the mRNA composition of axons, notably upregulating expression of mRNAs involved in axon growth and synaptogenesis. The presence of transcripts for components of translation machinery in axons indicates that local protein translation is possible.
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Culturing neurons in a microfluidic chamber with long, narrow channels enables isolation of axons (green) from somata and dendrites (yellow). See the article by Taylor et al. for details.
Behavioral/Systems/Cognitive
Methylphenidate Effects on Striatum and Behavior Are Correlated
Philip L. Clatworthy, Simon J. G. Lewis, Laurent Brichard, Young T. Hong, David Izquierdo, Luke Clark, Roshan Cools, Franklin I. Aigbirhio, Jean-Claude Baron, Timothy D. Fryer, and Trevor W. Robbins
(see pages 4690–4696)
Methylphenidate, a stimulant commonly used to treat attention deficit hyperactivity disorder, blocks the dopamine transporter, decreasing dopamine reuptake and increasing dopamine concentration in the synaptic cleft. The effects of methylphenidate are variable across tasks and individuals, however, and 25–35% of children do not respond to the drug. To investigate the basis of this variability, Clatworthy et al. used position emission tomography to measure methylphenidate-induced decreases in binding of radiolabeled D2/D3 receptor antagonist in striatal subregions of healthy adults, and then correlated inferred increases in synaptic dopamine levels with subjects' performance on reversal learning and spatial memory tasks. Performance on the reversal task was negatively correlated with changes in the postcommissural caudate: subjects with smaller drug-induced changes performed better, whereas those that had larger changes performed worse after treatment. In contrast, performance on the spatial memory task was positively correlated with changes in the ventral striatum: the bigger the drug-induced change, the better the performance.
Neurobiology of Disease
Delaying Plaque Formation Slows Subsequent Growth
Rachel A. Karlnoski, Arnon Rosenthal, Dione Kobayashi, Jaume Pons, Jennifer Alamed, Mary Mercer, Qingyou Li, Marcia N. Gordon, Paul E. Gottschall, and David Morgan
(see pages 4964–4971)
The plaques that characterize Alzheimer's disease are generally thought to grow gradually over years, as slight excesses of amyloid β protein are deposited. But when plaques are cleared in mice, they quickly return, suggesting that amyloid deposition increases with age. To distinguish between these alternatives, Karlnoski et al. injected anti-amyloid antibodies into amyloid-accumulating mice, starting when mice were 8 months old (before plaques were detectable) and continuing for 6 months. Mice treated with antibodies had significantly fewer plaques at 14 months than controls, indicating that antibody treatment successfully prevented amyloid accumulation. Over the next 3 months (without antibody treatment), amyloid deposits grew in all mice, but the deposits remained significantly smaller in mice that had previously been treated with anti-amyloid antibodies. The data suggest that unlike clearing existing plaques, preventing initial plaque formation can slow post-treatment amyloid accumulation. This supports the hypothesis that the initial deposition of amyloid "seeds" is a rate-limiting step in plaque formation.
Related articles in J. Neurosci.:
- Dopamine Release in Dissociable Striatal Subregions Predicts the Different Effects of Oral Methylphenidate on Reversal Learning and Spatial Working Memory
- Philip L. Clatworthy, Simon J. G. Lewis, Laurent Brichard, Young T. Hong, David Izquierdo, Luke Clark, Roshan Cools, Franklin I. Aigbirhio, Jean-Claude Baron, Timothy D. Fryer, and Trevor W. Robbins
J. Neurosci. 2009 29: 4690-4696.[Abstract] [Full Text] - Axonal mRNA in Uninjured and Regenerating Cortical Mammalian Axons
- Anne M. Taylor, Nicole C. Berchtold, Victoria M. Perreau, Christina H. Tu, Noo Li Jeon, and Carl W. Cotman
J. Neurosci. 2009 29: 4697-4707.[Abstract] [Full Text] - The Fast and Slow Afterhyperpolarizations Are Differentially Modulated in Hippocampal Neurons by Aging and Learning
- Elizabeth A. Matthews, John M. Linardakis, and John F. Disterhoft
J. Neurosci. 2009 29: 4750-4755.[Abstract] [Full Text] - Suppression of Amyloid Deposition Leads to Long-Term Reductions in Alzheimer's Pathologies in Tg2576 Mice
- Rachel A. Karlnoski, Arnon Rosenthal, Dione Kobayashi, Jaume Pons, Jennifer Alamed, Mary Mercer, Qingyou Li, Marcia N. Gordon, Paul E. Gottschall, and David Morgan
J. Neurosci. 2009 29: 4964-4971.[Abstract] [Full Text]
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