News Tips From The Journal Of Neuroscience

1. Homer is a Foursome

Mariko Kato Hayashi, Heather M. Ames, and Yasunori Hayashi

The long forms of the scaffolding protein, Homer, use their N-terminal EVH1 domain to interact with postsynaptic proteins such as metabotropic glutamate receptors (mGluRs), IP3 receptors and TRPC channels. The C-terminal coil-coiled domain allows oligomerization of Homer monomers. The short form, Homer1a, lacks the coiled-coil domains. This week, Hayashi et al. report that the long form, Homer1b, forms tetramers with all subunits arranged in parallel. The authors used a series of biophysical and imaging measures to investigate oligomerization. The linear tetramer makes it possible for Homer to act as a hub that can bring together different ligands to form signal transduction complexes. This arrangement is consistent with the known actions of Homer, for example, in linking mGluR1/5 to a downstream effector, the IP3 receptor. The Homer tetramer also interacts with another scaffolding protein, Shank. Shank forms antiparallel homodimers, thus Homer鈥揝hank complexes could potentially form large three-dimensional lattices.

2. NAD to the Rescue

Yo Sasaki, Toshiyuki Araki, and Jeffrey Milbrandt

This week, Sasaki et al. tested the role of nicotinamide adenine dinucleotide (NAD) in protecting neurons from axonal degeneration. NAD acts as a cofactor for most dehydrogenases and is involved in aerobic and anaerobic ATP generation. Previous studies have indicated that overexpression of nicotinamide mononucleotide adenylyltransferase1 (Nmnat1) can protect cultured dorsal root ganglion neurons from mechanical- or neurotoxin-induced axonal degeneration. The authors tested each step in the biosynthetic pathways that can generate NAD. They expressed the biosynthetic enzymes using lentiviral constructs in DRG neurons, then assayed their effects on axonal degeneration 24-72 h following axotomy. Nmnat1 had the strongest protective effect. However, nicotinamide phosphoribosyl transferase (NmPRT) and nicotinic acid phosphoribosyl transferase (NaPRT), which convert the precursor molecules nicotinamide and nicotinic acid to mononucleotides, also were protective when their respective substrates were present in the culture medium. Likewise, exogenous application of NAD precursors delayed axonal degeneration.

3. Discriminating Whiskers

Per Magne Knutsen, Maciej Pietr, and Ehud Ahissar

Rodents are adept at using their whiskers to localize and identify objects, and come equipped with the built-in ability to protract/retract and control whisker movements. This week, Knutsen et al. tested just how discriminating rats can be. Rats were trained to discriminate the relative horizontal offset of two vertical poles. Mango-flavored fruit juice was the reward. Both rats with all their whiskers intact, as well as partially shaved rats were tested. At least a single row of intact whiskers was required for task learning, but subsequent removal of whiskers did not affect the ability to discriminate. Active whisking was required for accurate localization with discrimination occurring in a 500 ms time window that corresponded to approximately four contacting whiskers. Rats were able to sense offsets down to 0.24 mm, or about 10% of spacing between whiskers. The authors refer to the active process that allows detection at finer resolution than whisker spacing as "vibrissal hyperacuity."

4. CB1 Receptors and Drug Seeking in Rats

Zheng-Xiong Xi, Jeremy G. Gilbert, Xiao-Qing Peng, Arlene C. Pak, Xia Li, and Eliot L. Gardner

Cannabinoid CB1 receptors are located on presynaptic nerve terminals in the nucleus accumbens (NAc), and are thus in position to affect the enhanced dopamine transmission that is critical in drug reward. This week, Xi et al. tested the action of the CB1 antagonist, AM251, on cocaine-primed reinstatement. Rats pressed a lever to self-administer cocaine through implanted catheters. Then they were exposed to extinction procedures (saline replaced cocaine, and cocaine-associated cues were removed) until lever pressing abated. Reinstatement of drug seeking was triggered by a priming injection of cocaine. AM251 inhibited this reinstatement, but not sucrose-mediated reinstatement. AM251 alone increased extracellular glutamate in the NAc and a metabotropic glutamate receptor (mGluR) 2/3 antagonist attenuated the effect of AM251 on reinstatement. Thus the authors propose a cascade in which the AM251 block of CB1 receptors leads to increased release of glutamate, activation of presynaptic mGluR2/3 autoreceptors, and the inhibition of cocaine-induced increases in NAc glutamate.

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News Tips From The Journal Of Neuroscience