Silva et al. show that CREB modulates allocation of fear memory to specific cells in the lateral amygdala. Reversibly inactivating a subset of CREB-expressing neurons disrupted memory for tone conditioning. Neurons with higher CREB levels were more excitable than their neighbors and showed larger synaptic efficacy changes following tone conditioning. The mechanisms that determine how information is allocated to specific regions and cells in the brain are important for memory capacity, storage and retrieval, but are poorly understood. We manipulated CREB in a subset of lateral amygdala neurons in mice with a modified herpes simplex virus (HSV) and reversibly inactivated transfected neurons with the Drosophila allatostatin G protein–coupled receptor (AlstR)/ligand system. We found that inactivation of the neurons transfected with HSV-CREB during training disrupted memory for tone conditioning, whereas inactivation of a similar proportion of transfected control neurons did not. Whole-cell recordings of fluorescently tagged transfected neurons revealed that neurons with higher CREB levels are more excitable than neighboring neurons and showed larger synaptic efficacy changes following conditioning. Our findings demonstrate that CREB modulates the allocation of fear memory to specific cells in lateral amygdala and suggest that neuronal excitability is important in this process.

Although memory allocation is a subject of active research in computer science, little is known about how the brain allocates information within neural circuits. There is an extensive literature on how specific types of memory engage different parts of the brain, and how neurons in these regions process and store information. Until recently, however, the mechanisms that determine how specific cells and synapses within a neural circuit (and not their neighbors) are recruited during learning have received little attention. Recent findings suggest that memory allocation is not random, but rather specific mechanisms regulate where information is stored within a neural circuit. New methods that allow tagging, imaging, activation, and inactivation of neurons in behaving animals promise to revolutionize studies of brain circuits, including memory allocation. Results from these studies are likely to have a considerable impact on computer science, as well as on the understanding of memory and its disorders.

The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estrogen receptor ligand-binding domain LBD^G521R. Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBD^G521R-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of αCaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning.

Current strategies for wound care provide limited relief to millions of patients who suffer from burns, chronic skin ulcers or surgical-related wounds. The goal of this work is to develop an in situ deposition of a personalized nanofibrous dressing via a handy electrospinning (e-spinning) device and evaluate its properties related to skin wound care. MCM-41 type mesoporous silica nanoparticles decorated with silver nanoparticles (Ag-MSNs) were prepared by a facile and environmentally friendly approach, which possessed long-term antibacterial activity and low cytotoxicity. Poly-ε-caprolactone (PCL) incorporated with Ag-MSNs was successfully electrospun (e-spun) into nanofibrous membranes. These in situ e-spun nanofibrous membranes allowed the continuous release of Ag ions and showed broad-spectrum antimicrobial activity against two common types of pathogens, Staphylococcus aureus and Escherichia coli. In addition, the in vivo studies revealed that these antibacterial nanofibrous membranes could reduce the inflammatory response and accelerate wound healing in Wistar rats. The above results strongly demonstrate that such patient-specific dressings could be broadly applied in emergency medical transport, hospitals, clinics and at the patients’ home in the near future.

Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.