RESUMO
The production of fossil fuels, including oil, gas, and coal, retains a dominant share in US energy production and serves as a major anthropogenic source of methane, a greenhouse gas with a high warming potential. In addition to directly emitting methane into the air, fossil fuel production can release methane into groundwater, and that methane may eventually reach the atmosphere. In this study, we collected 311 water samples from an unconventional oil and gas (UOG) production region in Pennsylvania and an oil and gas (O&G) and coal production region across Ohio and West Virginia. Methane concentration was negatively correlated to distance to the nearest O&G well in the second region, but such a correlation was shown to be driven by topography as a confounding variable. Furthermore, sulfate concentration was negatively correlated with methane concentration and with distance to coal mining in the second region, and these correlations were robust even when considering topography. We hypothesized that coal mining enriched sulfate in groundwater, which in turn inhibited methanogenesis and enhanced microbial methane oxidation. Thus, this study highlights the complex interplay of multiple factors in shaping groundwater methane concentrations, including biogeochemical conversion, topography, and conventional fossil extraction.
Assuntos
Combustíveis Fósseis , Água Subterrânea , Campos de Petróleo e Gás , Metano , Região dos Apalaches , Carvão Mineral , SulfatosRESUMO
Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson's disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1(-/-)) mice. Younger (<1 year) DJ-1(-/-) mice were hypoactive and had mild gait abnormalities. Older DJ-1(-/-), however, showed decreased body weight and grip strength and more severe gait irregularities compared to wild-type littermates. The basal level of extracellular dopamine, evoked dopamine release and dopamine receptor D2 sensitivity appeared normal in the striatum of DJ-1(-/-) mice, which was consistent with similar results between DJ-1(-/-) and controls in behavioral paradigms specific for the dopaminergic system. An examination of spinal cord, nerve and muscle tissues failed to identify any pathological changes that were consistent with the noted motor deficits. Taken together, our findings suggest that loss of DJ-1 leads to progressive behavioral changes without significant alterations in nigrostriatal dopaminergic and spinal motor systems.
Assuntos
Comportamento Animal/fisiologia , Corpo Estriado/fisiologia , Proteínas Associadas aos Microtúbulos/deficiência , Proteínas Associadas aos Microtúbulos/genética , Substância Negra/fisiologia , Animais , Progressão da Doença , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/fisiologiaRESUMO
The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M(1)-M(5)). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M(2) muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M(2) muscarinic receptor gene (M(2)(-/-) mice). Comprehensive assessment of general health and the neurological function found no major differences between M(2)(-/-) and wild-type (M(2)(+/+)) mice. In the tests of learning and memory, M(2)(-/-) mice were impaired in the acquisition (trials to criterion), but not the retention (72h) of a passive avoidance task. In a novel open field, M(2)(-/-) mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M(2)(-/-) mice committed more errors in working memory than M(2)(+/+) mice. Reference memory did not differ between the genotypes. M(2)(-/-) mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M(2) receptor plays a critical role in specific components of cognitive abilities.
Assuntos
Deficiências da Aprendizagem/genética , Transtornos da Memória/genética , Receptor Muscarínico M2/deficiência , Análise de Variância , Animais , Aprendizagem da Esquiva/fisiologia , Comportamento Animal , Condicionamento Psicológico , Comportamento Exploratório/fisiologia , Medo , Feminino , Habituação Psicofisiológica , Masculino , Memória de Curto Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores Sexuais , Comportamento EspacialRESUMO
To understand the role of striatum in motor sequence learning, we trained rats to perform a series of tasks measuring speed and accuracy of responding to luminance cues presented as discriminative stimuli for single nose pokes or for sequences of nose pokes in a serial reaction time task. Habit (stimulus-response) learning was measured by comparing performances when stimuli were repeated (predictable) with when they were selected randomly (unpredictable). Sequences had defined start and end points and were limited to five nose pokes to minimize chunking. When sequences were repeated, response time (RT) increased for nose pokes initiating the sequence and decreased for nose pokes completing it. These effects developed incrementally across sessions, consistent with the time course of habit learning. Medial (mCPu), lateral, and complete (CPu) caudate-putamen lesions affected speed and accuracy of single nose poke responses, confirming the role of these areas in guiding responses with external sensory stimuli. None of these lesions affected the short-term increase in accuracy observed when single nose poke responses were repeated. Both mCPu and CPu lesions increased RTs for initiating sequential responses, effects that were exacerbated across sessions in which specific sequences were repeated. None of the lesions affected the gradual decrease in RT for nose pokes completing repeated sequences. Correlational analyses confirmed the relationship between the extent of dorsal striatal damage and the ability to respond to brief luminance cues and to initiate learned sequences. These results provide evidence implicating dorsal striatum in higher-level organizational aspects of learning reflected in planning that precedes the execution of learned action sequences.
Assuntos
Corpo Estriado/fisiologia , Tempo de Reação/fisiologia , Aprendizagem Seriada/fisiologia , Animais , Gânglios da Base/fisiologia , Condicionamento Operante/fisiologia , Masculino , Ratos , Ratos Long-EvansRESUMO
The neuropeptide galanin has been implicated in anxiety-related behaviors, cognition, analgesia, and feeding in rodents. Neuromodulatory actions of galanin are mediated by three G-protein coupled receptors, GalR1, GalR2, and GalR3. The present study investigates the role of the GalR2 receptor by evaluating behavioral phenotypes of mice with a targeted mutation in the GalR2 gene. A three-tiered behavioral phenotyping approach first examined control measures of general health, body weight, neurological reflexes, sensory abilities and motor function. Mice were then assessed on several tests for cognitive and anxiety-like behaviors. GalR2 null mutants and heterozygotes were not significantly different from wildtype littermates on two cognitive tests previously shown to be sensitive to galanin manipulation: acquisition of the Morris water maze spatial task, and trace cued and contextual fear conditioning, an emotional learning and memory task. Two independent cohorts of GalR2 null mutant mice demonstrated an anxiogenic-like phenotype in the elevated plus-maze. No genotype differences were detected on several other measures of anxiety-like behavior. The discovery of an anxiogenic phenotype specific to the elevated plus-maze, similar to findings in GalR1 null mutants, highlights the potential therapeutic efficacy of targeting GalR1 and GalR2 receptors in treating anxiety disorders.
Assuntos
Ansiedade/genética , Ansiedade/psicologia , Receptor Tipo 2 de Galanina/genética , Receptor Tipo 2 de Galanina/fisiologia , Animais , Peso Corporal/fisiologia , Condicionamento Psicológico/fisiologia , Comportamento Exploratório/fisiologia , Medo/fisiologia , Medo/psicologia , Feminino , Genótipo , Saúde , Heterozigoto , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Knockout , Movimento/fisiologia , Dor/genética , Dor/psicologia , Medição da Dor , Fenótipo , Equilíbrio Postural/fisiologia , Reflexo/fisiologia , Sensação/fisiologia , Estresse Psicológico/genética , Estresse Psicológico/psicologiaRESUMO
New technologies in molecular genetics have dramatically increased the number of targeted gene mutations available to the biomedical research community. Many mutant mouse lines have been generated to provide animal models for human genetic disorders, offering insights into anatomical, neurochemical, and behavioral effects of aberrant gene expression. A variety of assays have been developed to identify and characterize phenotypic changes. In the behavioral domain, our phenotyping strategy involves a comprehensive standardized methodological approach that assesses general health, reflexes, sensory abilities, and motor functions. This assessment is followed by a series of complementary tasks in the specific behavioral domain(s) hypothesized to reveal the function(s) of the gene. Our multitiered approach minimizes intersubject variability by standardizing the experimental history for all animals, improves interlaboratory reliability by providing a clearly defined experimental protocol, and minimizes artifactual interpretations of behavioral data by careful preliminary assessments of basic behaviors, followed by multiple tests within the behavioral domain of interest. Despite meticulous attention to experimental protocol, attention to environmental factors is essential. Differences in noise, light, home cage environment, handling, and diet can dramatically alter behavior. Baseline differences in the behaviors of inbred strains used to generate targeted mutant mouse lines can directly influence the behavioral phenotype of the mutant line. Strategies aimed at minimizing environmental variability and contributions of background genes will enhance the robustness of mouse behavioral phenotyping assays.
Assuntos
Comportamento Animal/fisiologia , Camundongos Knockout/fisiologia , Criação de Animais Domésticos , Animais , Feminino , Abrigo para Animais , Masculino , Camundongos , Camundongos Knockout/genética , Camundongos Knockout/psicologia , FenótipoRESUMO
Three studies compared lesions of specific mediodorsal (MD) and nonspecific midline/intralaminar (M/IL) and ventromedial (VM) thalamic nuclei placed to spare the anterior nuclei. Lesions of MD, M/IL, or VM impaired delayed matching trained with retractable levers, a measure of spatial memory affected by prefrontal cortical lesions. The effects of the MD lesion increased at longer retention intervals and thus appeared delay dependent. The effects of M/IL and VM lesions were delay independent. Even when combined, these lesions had no effect on varying choice radial maze delayed nonmatching, a task sensitive to hippocampal or anterior thalamic (but not prefrontal) lesions. These results demonstrate effects of MD, M/IL, and VM lesions distinct from the contributions of hippocampus or anterior thalamus to spatial memory.
Assuntos
Memória/fisiologia , Córtex Pré-Frontal/fisiologia , Percepção Espacial , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiologia , Animais , Hipocampo/fisiologia , Masculino , Ratos , Ratos Long-EvansRESUMO
Ventral pallidum (VP) is an important source of limbic input to medial thalamus. Three studies examined the role of VP in spatial memory tasks impaired by medial thalamic lesions. In the 1st study, rats with VP lesions were impaired performing delayed matching trained with retractable levers (DMRL), a measure sensitive to prefrontal (but not hippocampal) damage. The 2nd study demonstrated dose-dependent DMRL impairment following microinjection of gamma-aminobutyric acidA, glutamate, or mu-opioid agonists in VP. In the 3rd study, VP lesions had no effect on varying choice radial-maze delayed nonmatching, a measure sensitive to hippocampal (but not prefrontal) lesions. These results suggest a common role in spatial memory for VP and other components of prefrontal-ventral striatopallidothalamic circuits distinct from hippocampal function.
Assuntos
Globo Pálido/fisiologia , Memória/fisiologia , Percepção Espacial , Animais , Globo Pálido/patologia , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/farmacologia , Masculino , Ratos , Ratos Long-Evans , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiologia , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/farmacologiaRESUMO
RATIONALE: The locus coeruleus (LC) is the source of norepinephrine (NE) in the prefrontal cortex (PFC) and hippocampus and may influence cognitive functions of these areas. Chronic effects of LC-NE lesions do not correspond consistently with acute effects of systemic or intracortical injections of adrenergic agents. OBJECTIVE: These studies aim to manipulate LC activity pharmacologically and study acute effects on measures of attention and memory that depend on the PFC and hippocampus. METHODS: Rats were trained to criterion for one of three tasks: visuospatial reaction time (VSRT), a measure of attention sensitive to PFC lesions, delayed matching trained with retractable levers (DM-RL), and delayed nonmatching trained in radial mazes (DNM-RM), measures of spatial working memory sensitive to PFC and hippocampal lesions, respectively. LC activity was manipulated with bilateral 0.5-microl injections of the alpha-2 agonist clonidine (0, 1.1, 4.5, and 18 nmol). RESULTS: Clonidine produced significant dose-dependent impairments of VSRT, affecting choice response time at the 18-nmol dose and choice accuracy at the 4.5- and 18-nmol doses. Clonidine had no effect on DMRL or DNM-RM at any of the doses tested. CONCLUSIONS: Reversible reduction of LC-NE activity by clonidine impaired measures of visuospatial attention sensitive to PFC lesions but were insufficient to affect PFC- or hippocampal-dependent measures of spatial working memory. These results are consistent with reports that LC-NE lesions produce chronic deficits in attention with little or no effect on measures of working memory.
Assuntos
Atenção/efeitos dos fármacos , Clonidina/farmacologia , Locus Cerúleo/efeitos dos fármacos , Memória/efeitos dos fármacos , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Clonidina/administração & dosagem , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/lesões , Hipocampo/fisiopatologia , Locus Cerúleo/lesões , Locus Cerúleo/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microinjeções/métodos , Norepinefrina/metabolismo , Fotomicrografia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/lesões , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos Long-Evans , Tempo de Reação/efeitos dos fármacos , Técnicas EstereotáxicasRESUMO
Galanin (GAL) impairs performance on cognitive tasks when administered centrally to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task. Knockout mice deficient in the GAL-R1 receptor subtype were normal on most memory tasks, while showing a small deficit in trace cued fear conditioning, suggesting a selective role for the GAL-R1 in aversive memories, and implicating other GAL receptor subtypes in spatial learning and olfactory social memory. The growing body of rodent literature implicating excess GAL in cognitive impairment is relevant to the overexpression of GAL in the basal forebrain during the progression of Alzheimer's disease.
Assuntos
Transtornos Cognitivos/fisiopatologia , Galanina/genética , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Receptor Tipo 1 de Galanina/genética , Animais , Galanina/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Receptor Tipo 1 de Galanina/metabolismoRESUMO
To understand the role of frontal cortex in motor sequence learning we compared the effects of motor (M1), premotor (M2) and midline frontal (MFr) cortical lesions on rats making nose-pokes guided by luminance cues. Organizational demands were manipulated by varying the number (1 vs. 5) and predictability (random vs. repeated) of nose-pokes in a response. Learning was studied by comparing sessions with random or repeated cues. All cortical lesions increased reaction time (RT) during response initiation. These effects were larger for nose-pokes initiating sequential responses but spared RT for nose-pokes completing them. Repetition learning had significant effects on the speed and accuracy of single nose-poke responses that were unaffected by any of the cortical lesions. Repetition learning had more complex effects on sequential responding. RTs increased for nose-pokes initiating sequences over several sessions of continuous repetition and then decreased or leveled off. RTs decreased incrementally across all repetition sessions for subsequent nose-pokes in repeated sequences, following a time-course consistent with habit learning. Lesions involving M2 and MFr cortex exacerbated the increase in RT during initiation without affecting the incremental decrease in RT for nose-pokes completing repeated sequences. These results were confirmed by analyses of interference effects when training shifted from repeated (learned) to random (novel) sequences or to a new repeated sequence. These results implicate dorsomedial frontal cortex in organizational aspects of sensory-guided responding and motor sequence learning reflected in RT during response initiation.