Reversible Plasticity of Fear Memory-Encoding Amygdala Synaptic Circuits Even after Fear Memory Consolidation

It is generally believed that after memory consolidation, memory-encoding synaptic circuits are persistently modified and become less plastic. This, however, may hinder the remaining capacity of information storage in a given neural circuit. Here we consider the hypothesis that memory-encoding synaptic circuits still retain reversible plasticity even after memory consolidation. To test this, we employed a protocol of auditory fear conditioning which recruited the vast majority of the thalamic input synaptic circuit to the lateral amygdala (T-LA synaptic circuit; a storage site for fear memory) with fear conditioning-induced synaptic plasticity. Subsequently the fear memory-encoding synaptic circuits were challenged with fear extinction and re-conditioning to determine whether these circuits exhibit reversible plasticity. We found that fear memory-encoding T-LA synaptic circuit exhibited dynamic efficacy changes in tight correlation with fear memory strength even after fear memory consolidation. Initial conditioning or re-conditioning brought T-LA synaptic circuit near the ceiling of their modification range (occluding LTP and enhancing depotentiation in brain slices prepared from conditioned or re-conditioned rats), while extinction reversed this change (reinstating LTP and occluding depotentiation in brain slices prepared from extinguished rats). Consistently, fear conditioning-induced synaptic potentiation at T-LA synapses was functionally reversed by extinction and reinstated by subsequent re-conditioning. These results suggest reversible plasticity of fear memory-encoding circuits even after fear memory consolidation. This reversible plasticity of memory-encoding synapses may be involved in updating the contents of original memory even after memory consolidation

A universal description for the experimental behavior of salt-(in)dependent oligocation-induced DNA condensation

We report a systematic study of the condensation of plasmid DNA by oligocations with variation of the charge, Z, from +3 to +31. The oligocations include a series of synthetic linear ε-oligo(l-lysines), (denoted εKn, n = 3–10, 31; n is the number of lysines equal to the ligand charge) and branched α-substituted homologues of εK10: εYK10, εLK10 (Z = +10); εRK10, εYRK10 and εLYRK10 (Z = +20). Data were obtained by light scattering, UV absorption monitored precipitation assay and isothermal titration calorimetry in a wide range concentrations of DNA and monovalent salt (KCl, CKCl). The dependence of EC50 (ligand concentration at the midpoint of DNA condensation) on CKCl shows the existence of a salt-independent regime at low CKCl and a salt-dependent regime with a steep rise of EC50 with increase of CKCl. Increase of the ligand charge shifts the transition from the salt-independent to salt-dependent regime to higher CKCl. A novel and simple relationship describing the EC50 dependence on DNA concentration, charge of the ligand and the salt-dependent dissociation constant of the ligand–DNA complex is derived. For the ε-oligolysines εK3–εK10, the experimental dependencies of EC50 on CKCl and Z are well-described by an equation with a common set of parameters. Implications from our findings for understanding DNA condensation in chromatin are discussed

The effect of salt on oligocation-induced chromatin condensation

Condensation of model chromatin in the form of fully saturated 12-mer nucleosome arrays, induced by addition of cationic ligands (ε-oligolysines with charge varied from +4 to +11), was studied in a range of KCl concentrations (10–500 mM) using light scattering and precipitation assay titrations. The dependence of EC50 (ligand concentration at the midpoint of the array condensation) on CKCl displays two regimes, a salt-independent at low CKCl and a salt-dependent at higher salt concentrations. In the salt-dependent regime EC50 rises sharply with increase of CKCl. Increase of ligand charge shifts the transition from the salt-independent to salt-dependent regime to higher salt. In the nucleosome array system, due to the partial neutralization of the DNA charge by histones, a lower oligocation concentration is needed to provoke condensation in the salt-independent regime compared to the related case of DNA condensation by the same cation. In the physiological range of salt concentrations (CKCl = 50–300 mM), K+ ions assist array condensation by shifting EC50 of the ε-oligolysines to lower values. At higher CKCl, K+ competes with the cationic ligands, which leads to increase of EC50. Values of salt-dependent dissociation constant for the ε-oligolysine–nucleosome array interaction were obtained, by fitting to a general equation developed earlier for DNA, describing the dependence of EC50 on dissociation constant, salt and polyelectrolyte concentrations

Biophysical Properties and Supramolecular Structure of Self-Assembled Liposome/ε-Peptide/DNA Nanoparticles: Correlation with Gene Delivery

Using solid-phase synthesis, lysine can be oligomerized by a reaction of the peptide carboxylate with the ε-amino group to produce nontoxic, biodegradable cationic peptides, ε-oligo­(l-lysines). Here α-substituted derivatives of such ε-oligo­(l-lysines) containing arginine and histidine in the side chain were tested as vectors for in vitro gene delivery. Combination of ε-oligolysines with the cationic lipid DOTAP and plasmid DNA resulted in transfection efficiency exceeding that of DOTAP alone, without significant increase in cytotoxicity. Synchrotron small-angle X-ray scattering studies revealed self-assembly of the DOTAP, ε-oligolysines, and DNA to ordered lamellar complexes. High transfection efficiency of the nanoparticles correlates with increase in zeta potential above +20 mV and requires particle size to be below 500 nm. The synergistic effect of branched ε-oligolysines and DOTAP in gene delivery can be explained by the increase in surface charge and by the supramolecular structure of the DOTAP/ε-oligolysine/DNA nanoparticles

Polymer-Mediated Formation and Assembly of Silver Nanoparticles on Silica Nanospheres for Sensitive Surface-Enhanced Raman Scattering Detection

To impart a desired optical property to metal nanoparticles (NPs) suitable for surface-enhanced Raman scattering (SERS) applications, it is crucial to assemble them in two or three dimensions in addition to controlling their size and shape. Herein, we report a new strategy for the synthesis and direct assembly of Ag NPs on silica nanospheres (AgNPs-SiNS) in the presence of poly­(ethylene glycol) (PEG) derivatives such as PEG-OH, bis­(amino)-PEGs (DA-PEGs), and <i>O</i>,<i>O</i>′-bis­(2-aminopropyl)­PEG (DAP-PEG). They exhibited different effects on the formation of Ag NPs with variable sizes (10–40 nm) and density on the silica surface. As the molecular weight (MW) of DA-PEGs increased, the number of Ag NPs on the silica surface increased. In addition, DAP-PEG (MW of 2000), which has a 2-aminopropyl moiety at both ends, promoted the most effective formation and assembly of uniform-sized Ag NPs on a silica surface, as compared to the other PEG derivatives with the same molecular weight. Finally, we demonstrated that AgNPs-SiNS bearing 4-fluorobenzenethiol on its surface induced the strong SERS signal at the single-particle level, indicating that each hybrid particle has internal hot spots. This shows the potential of AgNPs-SiNS for SERS-based sensitive detection of target molecules

Reversible modification of T-LA synaptic efficacy within a fixed modification range.

<p><b>A</b>. <b>Left</b>, Ceiling of the behaviorally modifiable range assessed with pairing-induced LTP. Robust LTP was observed in the groups for which T-LA synaptic weights were predicted to be at the floor of the range (naïve, extinction, unpaired group 1 & 2), whereas LTP was occluded in the groups for which T-LA synaptic weights were expected to be at the ceiling (conditioned, reconditioned). <b>Right</b>, Floor of the range estimated with depotentiation. Depotentiation was observed in the groups for which T-LA synaptic weights were predicted to be at the ceiling (conditioned, reconditioned), whereas depotentiation was absent in the groups for which T-LA synaptic weights were expected to be at the floor (naïve, extinction, unpaired group 1 and 2). <b>B.</b> Summary of the results shown in Fig. 2A. To avoid possible bias, the experiments in Fig. 2A were performed with the experimenter blind to the behavioral group.</p

Behavioral procedures.

<p><b>A.</b> Schematic diagram for behavioral procedures. Conditioning was carried out for two consecutive days, followed by extinction (three days) and reconditioning (two days) in a distinct context. White and gray tones in the rectangles represent context A and B, respectively. On day eight, brain slices were acquired from rats, while a separate set of animals were tested for fear memory retention. <b>B.</b> Pooled behavioral results for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024260#pone-0024260-g002" target="_blank">Fig. 2</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024260#pone-0024260-g003" target="_blank">3</a>.</p