Cellular/Molecular
Neuronal d-Serine Enhances LTP
Dina Rosenberg, Samar Artoul, Adi C. Segal, Goren Kolodney, Inna Radzishevsky, et al.
(see pages 3533–3544)
Glutamatergic activation of NMDA receptors (NMDARs) requires binding of a coagonist, usually d-serine. Vesicular release of d-serine from astrocytes is required for hippocampal long-term-potentiation (LTP), suggesting that astrocytes participate in synaptic plasticity by releasing d-serine. But d-serine is synthesized by serine racemase, which is expressed primarily in glutamatergic neurons. To investigate the role of neuronally derived d-serine in NMDAR-dependent synaptic activity, Rosenberg et al. sought to interfere with d-serine transport by Asc-1, a neuron-specific transporter that exchanges d-serine with neutral amino acids. They discovered that d-isoleucine is transported by Asc-1 and that it competitively interferes with transport of d-serine. Exogenous d-isoleucine inhibited d-serine uptake by rat neurons without affecting astrocytic uptake, suggesting it acted specifically on Asc-1. Moreover, d-isoleucine increased release of endogenous d-serine by neurons, and thereby increased the magnitude of NMDAR-dependent LTP in CA1 of rat hippocampal slices. These data indicate that neurons might be able to regulate their own plasticity by releasing d-serine.
Development/Plasticity/Repair
Axonal mRNA Is Needed for Normal Elongation and Branching
Christopher J. Donnelly, Michael Park, Mirela Spillane, Soonmoon Yoo, Almudena Pacheco, et al.
(see pages 3311–3322)
Local translation of mRNAs in axons and dendrites enables rapid responses to local signaling events. A fraction of axonal β-actin is synthesized from axonal mRNA, but most β-actin enters the axon after being synthesized in the cell body. Surprisingly, however, somally translated β-actin cannot fully compensate for loss of axonally translated β-actin. Donnelly et al. previously found that reducing axonal transport of mRNAs by zipcode binding protein 1—which transports mRNAs encoding β-actin and the growth-associated protein GAP-43—reduced axonal length and branching in cultured rat dorsal root ganglion neurons. They now show that expressing β-actin mRNA that was transported to the axon by a different protein rescued the branching defect, but not the elongation defect in these cells. Expressing axonally targeted GAP-43 mRNA rescued elongation but not branching. But expressing soma-restricted mRNA rescued neither phenotype. Similarly, knocking down β-actin or GAP-43 reduced branching or elongation, respectively, and these phenotypes were rescued by expressing the appropriate axonally targeted mRNA, but not by soma-restricted mRNA.
Expressing axonally targeted GAP-43 mRNA rescued the elongation deficit in neurons in which transport via zipcode binding protein 1 was reduced. See the article by Donnelly et al. for details.
Systems/Circuits
Ethanol Has Opposite Effects on CRF1+ and CRF1− Neurons
Melissa A. Herman, Candice Contet, Nicholas J. Justice, Wylie Vale, and Marissa Roberto
(see pages 3284–3298)
Many of the behavioral effects of alcohol consumption stem from effects on GABAergic transmission, and alterations in GABAergic signaling are major contributors to the development of alcohol dependence. Most neurons in the central nucleus of the amygdala (CeA) are GABAergic, and ethanol increases GABA release in the CeA by acting on presynaptic CRF1 receptors. Because activation of CRF1 appears to contribute to the development and maintenance of addiction, Herman et al. examined the effects of GABA on CRF1-positive and CRF1-negative CeA neurons. Both CRF1+ and CRF1− neurons exhibited tonic currents mediated by GABAA receptors. But unlike CRF1+ neurons, which exhibited tonic currents at baseline, CRF1− neurons exhibited tonic currents only when ambient GABA levels were increased. Furthermore, whereas ethanol enhanced the tonic current and reduced spike frequency in CRF1− neurons, it increased spike frequency in CRF1+ neurons without affecting tonic currents. The data suggest that by increasing ambient GABA levels, ethanol inhibits CRF1− neurons that inhibit CRF1+ neurons, and thus disinhibits CRF1+ neurons.
Behavioral/Cognitive
Changing Spatial Cues Affects Proximal More Than Distal CA1
Andrea L. Hartzell, Sara N. Burke, Lan T. Hoang, James P. Lister, Crystal N. Rodriguez, et al.
(see pages 3424–3433)
As a rat navigates an environment, different neurons fire at different locations. In a given arena, a given place cell always fires in the same location, its place field; but place fields remap when rats enter new arenas. Place cell firing is also modulated by nonspatial cues, such as objects, so moving objects within an arena also changes neuronal firing patterns. Whereas spatial information enters the hippocampus via medial entorhinal cortex, which projects to proximal CA1, information about objects arrives via projections from the lateral entorhinal cortex to distal CA1. Therefore, one might expect that after moving a rat from an arena containing a given set of objects to a different arena containing the same objects, greater changes in activity patterns would occur in proximal than in distal CA1. Hartzell et al. demonstrated that this is the case by using the expression pattern of the early-immediate gene Arc to identify neurons that were active in the first arena, the second arena, or both.
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