Evidence for long-term potentiation in phospholipid membranes.

Biological supramolecular assemblies, such as phospholipid bilayer membranes, have been used to demonstrate signal processing via short-term synaptic plasticity (STP) in the form of paired pulse facilitation and depression, emulating the brain's efficiency and flexible cognitive capabilities. However, STP memory in lipid bilayers is volatile and cannot be stored or accessed over relevant periods of time, a key requirement for learning. Using droplet interface bilayers (DIBs) composed of lipids, water and hexadecane, and an electrical stimulation training protocol featuring repetitive sinusoidal voltage cycling, we show that DIBs displaying memcapacitive properties can also exhibit persistent synaptic plasticity in the form of long-term potentiation (LTP) associated with capacitive energy storage in the phospholipid bilayer.

Morphine and high-fat diet differentially alter the gut microbiota composition and metabolic function in lean versus obese mice.

There are known associations between opioids, obesity, and the gut microbiome, but the molecular connection/mediation of these relationships is not understood. To better clarify the interplay of physiological, genetic, and microbial factors, this study investigated the microbiome and host inflammatory responses to chronic opioid administration in genetically obese, diet-induced obese, and lean mice. Samples of feces, urine, colon tissue, and plasma were analyzed using targeted LC-MS/MS quantification of metabolites, immunoassays of inflammatory cytokine levels, genome-resolved metagenomics, and metaproteomics.

Fentanyl and neostigmine delivered to mouse prefrontal cortex differentially alter breathing.

Opioids impair many functions modulated by the prefrontal cortex (PFC), including wakefulness, cognition, and breathing. In contrast, cholinergic activity in the PFC increases wakefulness. This study tested the hypothesis that microinjecting the opioid fentanyl and the acetylcholinesterase inhibitor neostigmine into the PFC of awake C57BL/6J male mice (n = 27) alters breathing.

Buprenorphine differentially alters breathing among four congenic mouse lines as a function of dose, sex, and leptin status.

The opioid buprenorphine alters breathing and the cytokine leptin stimulates breathing. Obesity increases the risk for respiratory disorders and can lead to leptin resistance. This study tested the hypothesis that buprenorphine causes dose-dependent changes in breathing that vary as a function of obesity, leptin status, and sex.

Opioids cause dissociated states of consciousness in C57BL/6J mice.

The electroencephalogram (EEG) provides an objective, neural correlate of consciousness. Opioid receptors modulate mammalian neuronal excitability, and this fact was used to characterize how opioids administered to mice alter EEG power and states of consciousness. The present study tested the hypothesis that antinociceptive doses of fentanyl, morphine, or buprenorphine differentially alter the EEG and states of sleep and wakefulness in adult, male C57BL/6J mice.

Prefrontal Cortex Metabolome Is Modified by Opioids, Anesthesia, and Sleep.

Obtundation of wakefulness caused by opioids and loss of wakefulness caused by anesthetics and sleep significantly alter concentrations of molecules comprising the prefrontal cortex (PFC) metabolome. Quantifying state-selective changes in the PFC metabolome is essential for advancing functional metabolomics. Diverse functions of the PFC suggest the PFC metabolome as a potential therapeutic entry point for countermeasures to state-selective autonomic dysfunction.

Neuronal mechanisms underlying opioid-induced respiratory depression: our current understanding.

Opioid-induced respiratory depression (OIRD) represents the primary cause of death associated with therapeutic and recreational opioid use. Within the United States, the rate of death from opioid abuse since the early 1990s has grown disproportionally, prompting the classification as a nationwide "epidemic." Since this time, we have begun to unravel many fundamental cellular and systems-level mechanisms associated with opioid-related death.

Isoflurane anesthesia disrupts the cortical metabolome.

Identifying similarities and differences in the brain metabolome during different states of consciousness has broad relevance for neuroscience and state-dependent autonomic function. This study focused on the prefrontal cortex (PFC) as a brain region known to modulate states of consciousness. Anesthesia was used as a tool to eliminate wakefulness.

Neurotransmitter networks in mouse prefrontal cortex are reconfigured by isoflurane anesthesia.

This study quantified eight small-molecule neurotransmitters collected simultaneously from prefrontal cortex of C57BL/6J mice ( = 23) during wakefulness and during isoflurane anesthesia (1.3%). Using isoflurane anesthesia as an independent variable enabled evaluation of the hypothesis that isoflurane anesthesia differentially alters concentrations of multiple neurotransmitters and their interactions.

Computer-based Multitaper Spectrogram Program for Electroencephalographic Data.

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. This paper describes a Windows-based, open source code for creating EEG multitaper spectrograms. The compiled program is accessible to Windows users without software licensing.

Opioid use in pregnancy: Borderline features and Hepatitis C virus.

This study examined the relationship between borderline personality disorder assessed as self-reported borderline features (Morey, 1991), opioid use, and Hepatitis C virus (HCV) in pregnant women. There were 55 women in the opioid use group and 38 in the comparison group who were at high risk due to medical issues that did not include drug use. Women were in their 2nd or 3rd trimester.

Promoting sleep and circadian health may prevent postoperative delirium: A systematic review and meta-analysis of randomized clinical trials.

This systematic review with meta-analysis and trial sequential analysis of randomized clinical trials aimed to clarify the efficacy of sleep and circadian interventions on preventing postoperative delirium. The search and screening identified 13 trials with great heterogeneity in interventions, surgery types as well as methods for evaluating delirium, sleep and circadian rhythms. Meta-analyses revealed that sleep and circadian interventions were associated with decreased incidences of postoperative delirium (pooled relative risk (RR) = 0.

Sleep fragmentation delays wound healing in a mouse model of type 2 diabetes.

Study Objectives: This study tested the hypothesis that sleep fragmentation (SF) delays wound healing in obese B6.BKS(D)-Leprdb/J (db/db) mice with impaired leptin signaling and type 2 diabetes compared with wild-type C57BL/6J (B6) mice.

Methods: Adult male mice (n = 34) were anesthetized and bilateral full-thickness excisional wounds were created on the back of each mouse.

Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep.

By identifying endogenous molecules in brain extracellular fluid metabolomics can provide insight into the regulatory mechanisms and functions of sleep. Here we studied how the cortical metabolome changes during sleep, sleep deprivation and spontaneous wakefulness. Mice were implanted with electrodes for chronic sleep/wake recording and with microdialysis probes targeting prefrontal and primary motor cortex.

Neurochemistry of Anesthetic States.

Anesthetic mechanisms that eliminate consciousness and perception of pain are products of the nervous system. Chemical approaches to the study of anesthetic mechanisms have the potential to serve as an ideal interface between basic and clinical neuroscience. There are disproportionately more basic neurochemical studies than clinical studies of anesthetic mechanisms.

Buprenorphine Depresses Respiratory Variability in Obese Mice with Altered Leptin Signaling.

Background: Opiate-induced respiratory depression is sexually dimorphic and associated with increased risk among the obese. The mechanisms underlying these associations are unknown. The present study evaluated the two-tailed hypothesis that sex, leptin status, and obesity modulate buprenorphine-induced changes in breathing.

Leptin status alters buprenorphine-induced antinociception in obese mice with dysfunctional leptin receptors.

Buprenorphine is an opiate used for pain management and to treat opiate addiction. The cytokine leptin can modulate nociception, but the extent to which buprenorphine-induced antinociception varies as a function of leptin signaling has not been characterized. Four congenic mouse lines with phenotypes that include differences in body weight and leptin status were used to test the hypothesis that the antinociceptive effects of buprenorphine vary as function of sex and leptin signaling.

RGS Proteins and Gαi2 Modulate Sleep, Wakefulness, and Disruption of Sleep/ Wake States after Isoflurane and Sevoflurane Anesthesia.

Study Objectives: This study tested the hypothesis that Regulators of G protein Signaling (RGS) proteins contribute to the regulation of wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, and to sleep disruption caused by volatile anesthetics.

Methods: The three groups used in this study included wild-type (WT; n = 7) mice and knock-in mice that were heterozygous (+/GS; n = 7) or homozygous (GS/GS; n = 7) for an RGS-insensitive allele that causes prolonged Gαi2 signaling. Mice were implanted with electrodes for recording sleep and conditioned for 1 week or more to sleep in the laboratory.

Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in Sprague Dawley rat.

Study Objectives: Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep.

Benzodiazepine site agonists differentially alter acetylcholine release in rat amygdala.

Background: Agonist binding at the benzodiazepine site of γ-aminobutric acid type A receptors diminishes anxiety and insomnia by actions in the amygdala. The neurochemical effects of benzodiazepine site agonists remain incompletely understood. Cholinergic neurotransmission modulates amygdala function, and this study tested the hypothesis that benzodiazepine site agonists alter acetylcholine (ACh) release in the amygdala.

Eszopiclone and dexmedetomidine depress ventilation in obese rats with features of metabolic syndrome.

Study Objectives: Obesity alters the therapeutic window of sedative/hypnotic drugs and increases the probability of respiratory complications. The current experiments used an established rodent model of obesity to test the hypothesis that the sedative/hypnotic drugs eszopiclone and dexmedetomidine alter ventilation differentially in obese rats compared with lean/fit rats.

Design: This study used a within-groups/between-groups experimental design.

GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation.

The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia and pain. The role of PnO γ-aminobutyric acid (GABA) in modulating these states remains incompletely understood. The present study used time to loss and time to resumption of righting response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness.

Thermal hyperalgesia after sciatic nerve block in rat is transient and clinically insignificant.

Ropivacaine has been associated with transient heat hyperalgesia in sciatic nerve blocks in rat. The goal of the present study was to evaluate the hypothesized presence of transient heat hyperalgesia after perineural injection of ropivacaine with a secondary subanalysis of 2 published studies. Paw withdrawal latency was used to assess the duration of sensory blockade and presence of heat hyperalgesia at 210, 240, 270, and 300 minutes and 24 hours after injection.

Adenosine A(1) receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release.

Background: Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release.