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The Journal of Neuroscience, August 1, 2007, 27(31)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Mixing and Matching NMDA Subunits
Rana A. Al-Hallaq, Thomas P. Conrads, Timothy D. Veenstra, and Robert J. Wenthold
(see pages 8334–8343)
Much has been written about the subunit composition of hippocampal NMDA receptors and their differential contributions to functions ranging from learning to neurodegeneration. Although NMDA receptors can be di-heteromeric, two NR1 subunits and two identical NR2 subunits, they can also be tri-heteromeric, containing NR1, NR2A, and NR2B subunits. Al-Hallaq et al. set out to examine receptors according to subunit content. The authors performed serial immunoprecipitations on membrane fractions from rat hippocampus. After depleting NR2A or NR2B, they quantified the remaining NR2-containing receptors. About two-thirds of total NR2A and NR2B subunits resided in di-heteromeric receptors, and one-third in tri-heteromeric receptors. Membrane-associated guanylate kinases bound equally to receptors containing NR2A or NR2B, but several synapse-associated proteins associated preferentially with NR2A, whereas collapsin response mediator protein 2 favored NR2B. End of story? Probably not, because only a fraction of NMDA receptors in mature animals could be extracted; thus synaptic receptors may have been underrepresented.
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The flowchart outlines serial immunoprecipitations used to separate di-heteromeric receptors and their associated proteins. The IP II Unbound fraction corresponds to the NR2A- or NR2B-di-heteromeric populations. See the article by Al-Hallaq et al. for details.
Development/Plasticity/Repair
Intrinsic Membrane Properties and Homeostatic Regulation
Kara G. Pratt and Carlos D. Aizenman
(see pages 8268–8277)
Remaining flexible (plastic) in response to ongoing neuronal activity is not limited to synapses, as Pratt and Aizenman demonstrate this week. The authors examined the intrinsic membrane excitability of tadpole optic tectal neurons during the period from early synapse formation (stage 42/43) to stage 49, when tectal field receptive fields become more refined. Measured sodium current amplitudes increased slightly between stage 42/43 and 44–46 and then declined by stage 49. The depolarization required to reach spike threshold was also lower at stage 44–46 than at stage 49. This period was also marked by increases in spontaneous synaptic activity, suggesting an inverse correlation between synaptic drive and intrinsic excitability. The authors tested this relationship by manipulating tectal neuron excitability in two ways: by overexpressing a leak potassium channel or by inhibiting AMPA receptor trafficking. In both cases, there was a compensatory increase in membrane excitability as a result of increased amplitude of voltage-gated sodium currents.
Behavioral/Systems/Cognitive
From Ribbon Synapses to Spike Trains
Peter Heil, Heinrich Neubauer, Dexter R. F. Irvine, and Mel Brown
(see pages 8457–8474)
This week, Heil et al. examined the output of the ribbon synapse between hair cells and primary afferent auditory-nerve (AN) fibers in the absence of auditory stimuli. They recorded the spike activity in single AN fibers in anesthetized cats, then used the distributions of the interspike intervals (ISIs) to model spontaneous release. Taking into account the spontaneous discharge rate and characteristic frequency of firing, the authors adjusted their models until they found one that reliably predicted the ISI distribution. The models assumed that excitatory release events occurred at random times and that each event caused a spike unless the fiber was refractory. Their results suggest that spontaneous release from the ribbon can be described as a homogeneous stochastic process with interevent distributions composed of an exponential and gamma component, with a modification to account for spike refractory periods. This model provided a better fit than the previously proposed Poisson release model.
Neurobiology of Disease
A Mediator of Neuronal Vulnerability in Dopamine Neurons
Chee Yeun Chung, James B. Koprich, Shogo Endo, and Ole Isacson
(see pages 8314–8323)
Although similar in many ways, dopaminergic neurons of the substantia nigra (SN, A9) and the ventral tegmental area (VTA, A10) differ in their vulnerability to cell death in Parkinson's disease (PD). Chung et al. show this week that G-substrate, an endogenous inhibitor of the serine/threonine phosphatases PP2A and PP1, may confer protection to A10 neurons. G-substrate got its name because it was first identified as a substrate for cGMP-dependent protein kinase. In rats and humans, A10 neurons expressed up to three times more G-substrate than A9 neurons. Overexpression of wild-type G-substrate protected dopaminergic neurons from 6-hydroxydopamine-induced toxicity. The T123A G-substrate mutant, which has reduced inhibition of PP2A, provided a lesser degree of neuroprotection. Unexpectedly, expression of G-substrate elevated baseline PP2A activity but blunted the PP2A activity surge following 6-hydroxydopamine. Among targets of PP2A, the authors' evidence suggests that increases in phosphorylated Akt may mediate the protective effects of G-substrate.
Related articles in J. Neurosci.:
- Homeostatic Regulation of Intrinsic Excitability and Synaptic Transmission in a Developing Visual Circuit
- Kara G. Pratt and Carlos D. Aizenman
J. Neurosci. 2007 27: 8268-8277.[Abstract] [Full Text] - An Endogenous Serine/Threonine Protein Phosphatase Inhibitor, G-Substrate, Reduces Vulnerability in Models of Parkinson's Disease
- Chee Yeun Chung, James B. Koprich, Shogo Endo, and Ole Isacson
J. Neurosci. 2007 27: 8314-8323.[Abstract] [Full Text] - NMDA Di-Heteromeric Receptor Populations and Associated Proteins in Rat Hippocampus
- Rana A. Al-Hallaq, Thomas P. Conrads, Timothy D. Veenstra, and Robert J. Wenthold
J. Neurosci. 2007 27: 8334-8343.[Abstract] [Full Text] - Spontaneous Activity of Auditory-Nerve Fibers: Insights into Stochastic Processes at Ribbon Synapses
- Peter Heil, Heinrich Neubauer, Dexter R. F. Irvine, and Mel Brown
J. Neurosci. 2007 27: 8457-8474.[Abstract] [Full Text]
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