Forebrain glucocorticoid receptor overexpression alters behavioral encoding of hippocampal CA1 pyramidal cells in mice

Stress hormone signaling via the glucocorticoid receptor (GR) modulates vulnerability to stress-related disorders, but whether GR influences how the brain encodes contextual experience is unknown. Mice with lifelong GR overexpression in forebrain glutamatergic neurons (GRov) show increased sensitivity to environmental stimuli. This phenotype is developmentally programmed and associated with profound changes in hippocampal gene expression. We hypothesized that GR overexpression influences hippocampal encoding of experiences. To test our hypothesis, we performed in vivo microendoscopic calcium imaging of 1359 dorsal CA1 pyramidal cells in freely behaving male and female WT and GRov mice during exploration of a novel open field. We compared calcium amplitude and event rate as well as sensitivity to center location and mobility between genotypes. GRov neurons exhibited higher average calcium activity than WT neurons in the novel open field. While most neurons showed sensitivity to center location and/or mobility, GRov neurons were more likely to be sensitive to center location and less likely to be sensitive to mobility, as compared to WT neurons. More than one-third of behavior-selective GRov neurons were uniquely sensitive to location without mobility sensitivity; these uniquely center-sensitive neurons were rare in WT. We conclude that dorsal CA1 pyramidal cells in GRov mice show increased activity in a novel environment and preferentially encode emotionally salient behavior. This heightened sensitivity to a novel environment and preferential encoding of emotionally salient elements of experience could underlie differential stress vulnerability in humans with increased glucocorticoid sensitivity.

Calcium Imaging Reveals Fast Tuning Dynamics of Hippocampal Place Cells and CA1 Population Activity during Free Exploration Task in Mice

Hippocampal place cells are a well-known object in neuroscience, but their place field formation in the first moments of navigating in a novel environment remains an ill-defined process. To address these dynamics, we performed in vivo imaging of neuronal activity in the CA1 field of the mouse hippocampus using genetically encoded green calcium indicators, including the novel NCaMP7 and FGCaMP7, designed specifically for in vivo calcium imaging. Mice were injected with a viral vector encoding calcium sensor, head-mounted with an NVista HD miniscope, and allowed to explore a completely novel environment (circular track surrounded by visual cues) without any reinforcement stimuli, in order to avoid potential interference from reward-related behavior. First, we calculated the average time required for each CA1 cell to acquire its place field. We found that 25% of CA1 place fields were formed at the first arrival in the corresponding place, while the average tuning latency for all place fields in a novel environment equaled 247 s. After 24 h, when the environment was familiar to the animals, place fields formed faster, independent of retention of cognitive maps during this session. No cumulation of selectivity score was observed between these two sessions. Using dimensionality reduction, we demonstrated that the population activity of rapidly tuned CA1 place cells allowed the reconstruction of the geometry of the navigated circular maze; the distribution of reconstruction error between the mice was consistent with the distribution of the average place field selectivity score in them. Our data thus show that neuronal activity recorded with genetically encoded calcium sensors revealed fast behavior-dependent plasticity in the mouse hippocampus, resulting in the rapid formation of place fields and population activity that allowed the reconstruction of the geometry of the navigated maze.

Green Synthesis of Gold Nanoparticles: A Novel, Environment-Friendly, Economic, Safe Approach

Nanoparticles can be synthesised using a variety of methods. These approaches, on the other hand, are connected with the development of undesired byproducts that are both harmful and expensive. As a result, several attempts are being undertaken to develop unique, cost-effective, safe, and dependable "green" techniques for producing desirable nanoparticles. To develop a novel, environment-friendly, economic, safe approach to the synthesis of gold nanoparticles via the biological entity. Addition of aqueous gold chloride solution to the microwave-exposed aqueous extracellular Cassia tora leaf extract yielded poly shaped gold nanoparticles. The UV-vis. spectroscopic investigations are led to notice and affirm the formation of nanoparticles. FTIR studies are performed to affirm the role of a biomolecule in stabilizing the nanoparticles. X-beam diffraction study is utilized to affirm the crystalline nature of nanoparticles. The elemental characterization of the samples is regulated by EDX studies. The size and morphology of the synthesized nanoparticles are explored using HR-TEM analysis and FESEM. It is seen that the flavonoids which are separated during microwave warming of extracellular solution of the cassia tora leaves are liable for the biosynthesis of gold nanoparticles. The nanoparticle was noted to be well dispersed and polyshaped with a 20-60 nm range. The leaf extract based preparation of AuNP is more gainful since leaf is used instead of microorganism as many of the issues like pathogenicity, procedural maintenance of hygiene of cell culture and labor efforts can be overcome. The presence of flavonoids in the leaf was discovered by the examination of produced nanoparticles, suggesting that they may have fulfilled both reduction and stabilisation activities. The presented approach can be inferred to be cost-effective, environmentally friendly, and capable of manufacturing nanoparticles with desired physical and pharmacological properties.

The Role of Trait Impulsivity and Novelty-Seeking as Predisposing Factors to the Acquisition and Reinstatement of MDMA Self-Administration

<p>It has been suggested that the response to novelty and impulsivity predict the latency to acquisition and maintenance of drug self-administration, respectively. The aim of this thesis was to examine the relationship between these two traits and (1) the latency to acquisition and (2) maintenance (drug seeking) of 3,4-methylenedioxymethamphetamine (MDMA) self–administration. Impulsivity, measured as premature responding on the 5-choice serial reaction time task (5-CSRTT), and novelty seeking, measured as the locomotor response in a novel environment, were measured prior to self-administration. Due to characteristics of the rat strain and test equipment the 5-CSRTT was configurated in the first part of this study and modified from the standard version. Following training in this task animals were implanted with a siliastic catheter and were subsequently screened for their response to a novel environment prior to MDMA self-administration. Latency to acquisition was determined as the number of test sessions required to self-administer an initial criterion of 90 infusions of 1.0 mg/kg/infusion as well as an additional 150 infusions of 0.5 mg/kg/infusion MDMA. For some rats, the ability of MDMA (0, 5.0 or 10.0 mg/kg, IP) to produce drug seeking was subsequently measured and for others, impulsivity was again measured following self-administration. Novelty seeking predicted cocaine self-administration but was not significantly correlated with either the acquisition or drug-seeking measures of MDMA self-administration. Impulsivity was not significantly correlated with the latency to acquire self-administration of MDMA but was significantly and positively correlated with the magnitude of MDMA produced drug-seeking. Furthermore, MDMA self-administration produced a number of notable, but transient, deficits in the 5-CSRTT; there was an increase in omission rate and a delayed increase in premature responses in particular. These findings suggest that impulsivity, but not sensation seeking, might be a risk factor for the development of compulsive drug-seeking following withdrawal from MDMA self-administration. A surprising finding from this study was a high acquisition rate amongst rats that acquired the 5-CSRTT prior to self-administration. This difference was examined in a separate set of experiments. This effect could not be explained by an effect of handling, food restriction, or exposure to sweetened condensed milk and might possibly be due to differences in instrumental learning.</p>

The Role of Trait Impulsivity and Novelty-Seeking as Predisposing Factors to the Acquisition and Reinstatement of MDMA Self-Administration

<p>It has been suggested that the response to novelty and impulsivity predict the latency to acquisition and maintenance of drug self-administration, respectively. The aim of this thesis was to examine the relationship between these two traits and (1) the latency to acquisition and (2) maintenance (drug seeking) of 3,4-methylenedioxymethamphetamine (MDMA) self–administration. Impulsivity, measured as premature responding on the 5-choice serial reaction time task (5-CSRTT), and novelty seeking, measured as the locomotor response in a novel environment, were measured prior to self-administration. Due to characteristics of the rat strain and test equipment the 5-CSRTT was configurated in the first part of this study and modified from the standard version. Following training in this task animals were implanted with a siliastic catheter and were subsequently screened for their response to a novel environment prior to MDMA self-administration. Latency to acquisition was determined as the number of test sessions required to self-administer an initial criterion of 90 infusions of 1.0 mg/kg/infusion as well as an additional 150 infusions of 0.5 mg/kg/infusion MDMA. For some rats, the ability of MDMA (0, 5.0 or 10.0 mg/kg, IP) to produce drug seeking was subsequently measured and for others, impulsivity was again measured following self-administration. Novelty seeking predicted cocaine self-administration but was not significantly correlated with either the acquisition or drug-seeking measures of MDMA self-administration. Impulsivity was not significantly correlated with the latency to acquire self-administration of MDMA but was significantly and positively correlated with the magnitude of MDMA produced drug-seeking. Furthermore, MDMA self-administration produced a number of notable, but transient, deficits in the 5-CSRTT; there was an increase in omission rate and a delayed increase in premature responses in particular. These findings suggest that impulsivity, but not sensation seeking, might be a risk factor for the development of compulsive drug-seeking following withdrawal from MDMA self-administration. A surprising finding from this study was a high acquisition rate amongst rats that acquired the 5-CSRTT prior to self-administration. This difference was examined in a separate set of experiments. This effect could not be explained by an effect of handling, food restriction, or exposure to sweetened condensed milk and might possibly be due to differences in instrumental learning.</p>

Effects of exploring a novel environment on memory across the lifespan

Exploration is a crucial aspect of mammalian behavior, and new environments provide unique opportunities to learn. Exploration of a novel environment has been shown to promote memory formation in healthy adults, even for unrelated events. Studies in animals have suggested that such novelty-induced memory boosts are mediated by hippocampal dopamine. The dopaminergic system is known to develop and deteriorate over the lifespan, but so far, the effects of novelty on memory across the lifespan have not yet been investigated. In the current study, we used novel and previously familiarized virtual environments to pinpoint the effects of spatial novelty on declarative memory in humans across the lifespan. After exploring a novel or familiar environment, participants were presented a list of words, and either performed a semantic task (deep encoding) or judged whether the first letter of the shown word was open or closed (shallow encoding). Incidental memory was quantified in a surprise test. Our sample (n = 439) included children, adolescents, younger adults, and older adults. Results showed that participants in the deep encoding condition remembered more words than those in the shallow condition, but novelty did not influence this effect. Interestingly, however, children, adolescents and younger adults benefitted from exploring a novel compared to a familiar environment as evidenced by better word recall, while these effects were absent in older adults. Our findings suggest that the beneficial effects of novelty on memory follow the deterioration of pathways in the brain involved in novelty-related processing across the lifespan.