The effects of environmental enrichment on nicotine sensitization in a rodent model of schizophrenia

Environmental enrichment, for more than fifty years, has shown to increase learning in behaviors and to alter some brain structures (Renner and Rosenzweig). Some brain changes that occur when environmental enrichment is implemented include the following: increases in cortical thickness, especially the occipital cortex, increases in size of neuronal cell bodies, number of dendrites and dendritic spines, increases in astrocyte branching, increases in the number of brain blood capillaries, and increases in mitochondria (an indication of higher metabolic activity) (Stairs and Bard). It has been shown in research studies that rats in the environmental enrichment group are less sensitive to nicotine effects, both repeated and acute, than rats in isolated situations (Green et al). This is so because enrichment changes the intensity of the acute administration of drugs of abuse. Rats are stimulated by the environment, rather than a particular stimulant

Corticosterone Administration up-Regulated Expression of Norepinephrine Transporter and Dopamine Β-Hydroxylase in Rat Locus Coeruleus and Its Terminal Regions

Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. In this study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase in DBH protein levels only appeared in the hippocampus and the amygdala. Elevated NET and DBH expression in most of these areas (except for NET protein levels in the LC) was abolished by simultaneous treatment with combination of corticosteroid receptor antagonist mifepristone and spironolactone (s.c. for 21 days). Also, treatment with mifepristone alone prevented CORT-induced increases of NET expression and DBH protein levels in the LC. In addition, behavioral tasks showed that CORT ingestion facilitated escape in avoidance trials using an elevated T-maze, but interestingly, there was no significant effect on the escape trial. Corticosteroid receptor antagonists failed to counteract this response in CORT-treated rats. In the open-field task, CORT treatment resulted in less activity in a defined central zone compared to controls and corticosteroid receptor antagonist treatment alleviated this increase. In conclusion, this study demonstrates that chronic exposure to CORT results in a phenotype that mimics stress-induced alteration of noradrenergic phenotypes, but the effects on behavior are task dependent. As the sucrose consumption test strongly suggests CORT ingestion-induced depression-like behavior, further elucidation of underlying mechanisms may improve our understanding of the correlation between stress and the development of depression

Surface reconstruction of pure-Cu single-crystal electrodes under Co-reduction potentials in alkaline solutions: A study by seriatim ECSTM-DEMS

Quasi-operando electrochemical scanning tunneling microscopy (ECSTM) recently showed that a polycrystalline Cu electrode kept in 0.1 M KOH at − 0.9 V (SHE), a potential very close to that for electrochemical CO reduction, underwent a two-step surface reconstruction, initially to Cu(111), or Cu(pc)-[Cu(111)], and terminally to Cu(100), or Cu(pc)-[Cu(100)]. When subjected to monolayer-limited Cu_((s)) ↔ Cu_2O_((s)) oxidation-reduction cycles (ORC), the Cu(pc)-[Cu(100)] surface was further transformed to Cu(pc)-[Cu(511)] that produced C_2H_5OH exclusively, as detected by differential electrochemical mass spectrometry, at an overvoltage lower by 645 mV relative to that for the formation of hydrocarbons. In this paper, results are presented from studies with the native monocrystalline surfaces Cu(111), Cu(100) and Cu(110). Whereas the intermediate Cu(pc)-[Cu(111)] layer was eventually converted to Cu(pc)-[Cu(100)], the surface of a pristine Cu(111) single crystal itself showed no such conversion. The surface of an original Cu(100) electrode likewise proved impervious to potential perturbations. In contrast, the outer plane of a Cu(110) crystal underwent three transformations: first to disordered Cu(110)-d[Cu(110)], then to disordered Cu(110)-d[Cu(111)], and finally to an ordered Cu(110)-[Cu(100)] plane. After multiple ORC, the converted [Cu(100)] lattice atop the Cu(110) crystal did not generate ethanol, in contrast to the [Cu(100)] phase above the Cu(pc) bulk. Quasi-operando ECSTM captured the disparity: Post-ORC, Cu(110)-[Cu(100)] was converted, not to Cu(110)-[Cu(511)], but to an ordered but catalytically inactive Cu(110)-[Cu(111)]; hence, no C2H5OH production upon reduction of CO, as would have been the case for a stepped Cu(511) surface

The Effects of Nicotine in the Neonatal Quinpirole Rodent Model of Psychosis: Neural Plasticity Mechanisms and Nicotinic Receptor Changes

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1–21. Animals were given ip injections of either saline or nicotine (0.5 mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4 mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3 mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not 7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking

Dopamine transporter genotype is associated with a lateralized resistance to distraction during attention selection

Although lateral asymmetries in orienting behavior are evident across species and have been linked to interhemispheric asymmetries in dopamine signaling, the relative contribution of attentional versus motoric processes remains unclear. Here we took a cognitive genetic approach to adjudicate between roles for dopamine in attentional versus response selection. A sample of nonclinical adult humans (N = 518) performed three cognitive tasks (spatial attentional competition, spatial cueing, and flanker tasks) that varied in the degree to which they required participants to resolve attentional or response competition. All participants were genotyped for two putatively functional tandem repeat polymorphisms of the dopamine transporter gene (DAT1; SLC6A3), which are argued to influence the level of available synaptic dopamine and confer risk to disorders of inattention. DAT1 genotype modulated the task-specific effects of the various task-irrelevant stimuli across both the spatial competition and spatial cueing but not flanker tasks. Specifically, compared with individuals carrying one or two copies of the 10-repeat DAT1 allele, individuals without this allele demonstrated an immunity to distraction, such that response times were unaffected by increases in the number of distractor stimuli, particularly when these were presented predominantly in the left hemifield. All three genotype groups exhibited uniform costs of resolving leftward response selection in a standard flanker task. None of these significant effects could be explained by speed–accuracy trade-offs, suggesting that participants without the 10-repeat allele of the DAT1 tandem repeat polymorphism possess an enhanced attentional ability to suppress task-irrelevant stimuli in the left hemifield

The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms

Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain

Surface reconstruction of pure-Cu single-crystal electrodes under Co-reduction potentials in alkaline solutions: A study by seriatim ECSTM-DEMS

Quasi-operando electrochemical scanning tunneling microscopy (ECSTM) recently showed that a polycrystalline Cu electrode kept in 0.1 M KOH at − 0.9 V (SHE), a potential very close to that for electrochemical CO reduction, underwent a two-step surface reconstruction, initially to Cu(111), or Cu(pc)-[Cu(111)], and terminally to Cu(100), or Cu(pc)-[Cu(100)]. When subjected to monolayer-limited Cu_((s)) ↔ Cu_2O_((s)) oxidation-reduction cycles (ORC), the Cu(pc)-[Cu(100)] surface was further transformed to Cu(pc)-[Cu(511)] that produced C_2H_5OH exclusively, as detected by differential electrochemical mass spectrometry, at an overvoltage lower by 645 mV relative to that for the formation of hydrocarbons. In this paper, results are presented from studies with the native monocrystalline surfaces Cu(111), Cu(100) and Cu(110). Whereas the intermediate Cu(pc)-[Cu(111)] layer was eventually converted to Cu(pc)-[Cu(100)], the surface of a pristine Cu(111) single crystal itself showed no such conversion. The surface of an original Cu(100) electrode likewise proved impervious to potential perturbations. In contrast, the outer plane of a Cu(110) crystal underwent three transformations: first to disordered Cu(110)-d[Cu(110)], then to disordered Cu(110)-d[Cu(111)], and finally to an ordered Cu(110)-[Cu(100)] plane. After multiple ORC, the converted [Cu(100)] lattice atop the Cu(110) crystal did not generate ethanol, in contrast to the [Cu(100)] phase above the Cu(pc) bulk. Quasi-operando ECSTM captured the disparity: Post-ORC, Cu(110)-[Cu(100)] was converted, not to Cu(110)-[Cu(511)], but to an ordered but catalytically inactive Cu(110)-[Cu(111)]; hence, no C2H5OH production upon reduction of CO, as would have been the case for a stepped Cu(511) surface

Evaluation of Long-Range Lightning Detection Networks Using TRMM/LIS Observations

Recent advances in long-range lightning detection technologies have improved our understanding of thunderstorm evolution in the data sparse oceanic regions. Although the expansion and improvement of long-range lightning datasets have increased their applicability, these applications (e.g., data assimilation, atmospheric chemistry, and aviation weather hazards) require knowledge of the network detection capabilities. Toward this end, the present study evaluates data from the World Wide Lightning Location Network (WWLLN) using observations from the Lightning Imaging Sensor (LIS) aboard the Tropical Rainfall Measurement Mission (TRMM) satellite. The study documents the WWLLN detection efficiency and location accuracy relative to LIS observations, describes the spatial variability in these performance metrics, and documents the characteristics of LIS flashes that are detected by WWLLN. Improved knowledge of the WWLLN detection capabilities will allow researchers, algorithm developers, and operational users to better prepare for the spatial and temporal coverage of the upcoming GOES-R Geostationary Lightning Mapper (GLM)

The sensitivity of ECG contamination to surgical implantation site in brain computer interfaces.

BACKGROUND Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. OBJECTIVES Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. METHODS Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. RESULTS The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. CONCLUSIONS Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration