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Amnesic mice retain silent memory engrams

Hippocampal dentate gyrus engram cells (red) store fear memories.

Memory engrams refer to long-lasting, learning-induced physical or chemical changes that occur in brain networks. Researchers have shown that the reactivation of these engram cells, which are located in the dentate gyrus of the hippocampus, triggers the recollection of specific memories. Dheeraj Roy et al. (pp. E9972–E9979) demonstrate that engram cells in amnesic mice can also exist in an enduring silent state, in which memory information is retained and can be retrieved not by natural recall cues, but by strong stimulation with optogenetics—a technique that uses light to control the activity of genetically defined neurons. During the training session, the authors placed mice in a chamber with an electrified grid floor that delivered foot shocks. Immediately after fear learning, the authors injected the mice with either the amnesia-inducing molecule anisomycin or saline as a control. One day later, the control group froze in fear when reexposed to the shock chamber, which was filled with natural recall cues, whereas the anisomycin-treated mice showed significantly less freezing behavior. However, optogenetic stimulation of the engram cells 2–8 days after training triggered similarly high levels of freezing behavior in both control and anisomycin-treated mice. According to the authors, future studies on the properties of silent engrams could illuminate the formation and retrieval of memories. — J.W.

Odorant-binding proteins in the giant panda

Odorant-binding proteins of the giant panda bind putative pheromones and bamboo volatiles with complementary specificities.

Feeding and mating in the giant panda are regulated by pheromones and smell, both of which have been little explored at the molecular level in this species. A better understanding of pheromones could help improve conservation strategies for giant pandas. Jiao Zhu et al. (pp. E9802–E9810) identified six putative odorant-binding proteins (OBPs) in the giant panda genome, based on homology with OBPs from other mammals. Four of these proteins were detected in nasal mucus, consistent with a role in detecting chemical signals. The authors examined the binding specificity of two of these proteins—AimelOBP3 and AimelOBP5—that exhibited complementary binding patterns. The former protein exhibited high affinity to long-chain unsaturated aldehydes, found among pheromones in several butterfly species, and to plant volatile compounds that are abundant in bamboo leaves. The latter protein exhibited low affinity to these compounds, but high affinity to fatty acids, for which AimelOBP3 had low affinity. The authors solved the crystal structure of AimelOBP3 and generated variant proteins in which single amino acids were replaced in the putative binding site. The altered binding affinities of these variants suggested the mode of interaction between AimelOBP3 and its binding partners. According to the authors, the results could be used to identify candidate pheromones for the giant panda. — B.D.

Visualizing intercellular RNA transfer through membrane nanotubes

MicroRNAs and messenger RNA (mRNA) fragments can move between mammalian cells by diffusing through extracellular fluids in membrane-enclosed vesicles. Using single-molecule fluorescent in situ hybridization and live imaging, Gal Haimovich et al. (pp. E9873–E9882) observed the intercellular transfer of full-length mRNA molecules between animal cells grown together in laboratory dishes through an alternate mechanism. Rather than diffusing through extracellular fluids in vesicles, the mRNA molecules, including those for mouse actin and human BRCA1 and HER2, were transported through tunnel-like protrusions from the cell surface called membrane nanotubes, which are around 0.5 μm wide and up to 200 μm long. RNA transport through membrane nanotubes appears to be mediated by actin filaments and is dependent on direct physical contact between donor and acceptor cells. Further, gene expression changes and environmental stress appear to influence intercellular mRNA transfer. Because proteins synthesized from transferred mRNA molecules can influence the physiology of acceptor cells and because membrane nanotubes have been observed in tumors derived from cancer patients, the authors speculate that intercellular mRNA transport could alter tumor microenvironments and trigger or abet carcinogenesis. According to the authors, membrane nanotube-mediated RNA transfer might also influence other biological processes, such as embryonic development and tissue maintenance and regeneration. — P.N.

Waiting periods and gun deaths

Each year, more than 33,000 gun-related deaths occur in the United States. Waiting period laws have the potential to deter gun violence by delaying the acquisition of a firearm. Michael Luca et al. (pp. 12162–12165) compared the changes in the number of firearm-related deaths in states that enacted handgun waiting periods to the changes in the number of firearm-related deaths in states without waiting period laws from 1970 to 2014; 44 states including Washington, DC, had waiting periods at some point during this period. The authors find that waiting periods were associated with approximately 36 fewer gun homicides per year in a state with an average number of gun deaths. Waiting periods also were associated with 22–35 fewer gun suicides per year in a state with an average number of gun deaths. Furthermore, the authors conducted a supplemental analysis of the period from 1990 to 1998, during which a federal law—the Brady Act—required 19 states to adopt new handgun waiting periods. The authors found that waiting periods enacted during this time were associated with approximately 39 fewer gun homicides and approximately 17 fewer gun suicides per year for a state with an average number of gun deaths. The authors suggest that the 17 states, including Washington, DC, that had waiting periods as of 2014, likely avoid approximately 750 gun homicides per year with waiting period laws, and that passing waiting period laws in the remaining states might prevent more than 900 additional US gun homicides per year. — L.C.

Hippocampus and movement-related brain activity

In the rodent hippocampus, electrical activity during motion is dominated by 6–10-Hz theta frequency oscillations, the amplitude of which encodes movement-related information. To examine whether theta oscillations play a similar role in the human brain, Daniel Bush et al. (pp. 12297–12302) analyzed intracranial recordings from the temporal lobes of 13 presurgical epilepsy patients who were asked to navigate a computerized virtual environment. Focusing on signals related to movement initiation, the authors isolated a key cross-species parallel in neural activity: peaks in theta power in the hippocampus and lateral temporal lobe occurred around the time movement began after a stationary period. In addition, the analysis revealed that theta power in the human hippocampus reflects the distance to be travelled and remains relatively high across all periods of movement in a virtual environment. The findings suggest that insights into movement-related theta frequency activity in rodents can be applied to the human brain, expanding the growing body of work aimed at understanding how humans navigate their environment, according to the authors. — T.J.

Online Impact

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