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Behavioral Neuroscience Jun 2024In recent years, there have been significant advances in our understanding of the positive symptoms of schizophrenia, such as hallucinations and delusions. This progress... (Review)
Review
In recent years, there have been significant advances in our understanding of the positive symptoms of schizophrenia, such as hallucinations and delusions. This progress has been significantly aided by the use of associative learning-based approaches in human subjects and preclinical animal models. Here, we first review experimental research focusing on the abnormal processing of absent stimuli using three different conditioning phenomena: conditioned hallucinations, mediated conditioning, and trace conditioning. We then review studies investigating the ability to reduce focal processing of physically present but informationally redundant stimuli using habituation, latent inhibition, and blocking. The results of these different lines of research are then summarized within the framework of Wagner's (1981) standard operating procedures model, an associative learning model with explicit reference to the internal representations of both present and absent stimuli. Within this framework, the central deficit associated with positive symptoms can be described as a failure to suppress the focal processing of both absent stimuli and present but irrelevant stimuli. This can explain the wide range of results obtained in different experimental settings. Finally, we briefly discuss the role of the hippocampus and its interaction with dopaminergic transmission in the emergence of such abnormal stimulus representations and learning. Overall, we hope that the theoretical framework and empirical findings offered by the associative learning approach will continue to facilitate and integrate analyses of schizophrenia conducted at the psychological and behavioral levels on the one hand, and at the neural and molecular levels on the other, by serving as a useful interface between them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Topics: Humans; Association Learning; Schizophrenia; Animals; Psychotic Disorders; Hallucinations; Schizophrenic Psychology; Conditioning, Classical; Hippocampus; Perception
PubMed: 38934921
DOI: 10.1037/bne0000599 -
Behavioral Neuroscience Jun 2024A growing body of literature indicates that mediated learning techniques have specific utility for tapping into reality testing in animal models of neuropsychiatric...
A growing body of literature indicates that mediated learning techniques have specific utility for tapping into reality testing in animal models of neuropsychiatric illness. In particular, recent work has shown that animal models that recapitulate various endophenotypes of schizophrenia are particularly vulnerable to impairments in reality testing when undergoing mediated learning. Multiple studies have indicated that these effects are dopamine receptor 2-dependent and correlated with aberrant insular cortex (IC) activity. However, until now, the connection between dopamine and the IC had not been investigated. Here, we utilized a novel intersectional approach to label mesencephalic dopamine cells that specifically project to the insular cortex in both wild-type controls and transgenic mice expressing the dominant-negative form of the Disrupted-in-Schizophrenia-1 (DISC-1) gene. Using these techniques, we identified a population of cells that project from the ventral tegmental area (VTA) to the IC. Afterward, we conducted multiple studies to test the necessity of this circuit in behaviors ranging from gustatory detection to the maintenance of effort and, finally, mediated performance. Our results indicate that perturbations of the DISC-1 genetic locus lead to a reduction in the number of cells in the VTA → IC circuit. Behaviorally, VTA → IC circuitry does not influence gustatory detection or motivation to acquire sucrose reward; however, inactivation of this circuit differentially suppresses Pavlovian approach behavior in wild-type and DISC-1 transgenic mice during mediated performance testing. Moreover, under these testing conditions, inactivation of this circuit predisposes wild-type (but not DISC-1) mice to display impaired reality testing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Topics: Animals; Mice, Transgenic; Dopaminergic Neurons; Mice; Insular Cortex; Male; Ventral Tegmental Area; Mice, Inbred C57BL; Neural Pathways; Reward; Disease Models, Animal; Dopamine; Nerve Tissue Proteins; Mesencephalon; Schizophrenia
PubMed: 38934920
DOI: 10.1037/bne0000580 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that...
In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that obesogenic high-fat and sugar diet intake during adolescence (adoHFSD) impairs hippocampus (HPC)-dependent memory in rodents. These results were obtained in males only and it remains to evaluate whether adoHFSD has similar effect in females. Therefore, here, we investigated the effects of adoHFSD consumption on HPC-dependent contextual fear memory and associated brain activation in male and female mice. Exposure to adoHFSD increased fat mass accumulation and glucose levels in both males and females but impaired contextual fear memory only in males. Compared with females, contextual fear conditioning induced higher neuronal activation in the dorsal and ventral HPC (CA1 and CA3 subfields) as well as in the medial prefrontal cortex in males. Also, adoHFSD-fed males showed enhanced c-Fos expression in the dorsal HPC, particularly in the dentate gyrus, and in the basolateral amygdala compared with the other groups. Finally, chemogenetic inactivation of the dorsal HPC rescued adoHFSD-induced memory deficits in males. Our results suggest that males are more vulnerable to the effects of adoHFSD on HPC-dependent aversive memory than females, due to overactivation of the dorsal HPC.
Topics: Animals; Fear; Male; Female; Hippocampus; Diet, High-Fat; Obesity; Sex Characteristics; Mice; Memory; Mice, Inbred C57BL; Prefrontal Cortex
PubMed: 38934712
DOI: 10.1093/cercor/bhae254 -
Frontiers in Neural Circuits 2024Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral... (Review)
Review
Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral cortex, hippocampus, and retina. In the OB, the dendritic development of excitatory projection neurons like mitral/tufted cells is influenced by olfactory experiences. Odor stimulation is also essential for the dendritic development of inhibitory OB interneurons, such as granule and periglomerular cells, which are continuously produced in the ventricular-subventricular zone throughout life. Based on the morphological and molecular features, OB interneurons are classified into several subtypes. The role for each interneuron subtype in the control of olfactory behavior remains poorly understood due to lack of each specific marker. Among the several OB interneuron subtypes, a specific granule cell subtype, which expresses the oncofetal trophoblast glycoprotein (Tpbg or 5T4) gene, has been reported to be required for odor detection and discrimination behavior. This review will primarily focus on elucidating the contribution of different granule cell subtypes, including the Tpbg/5T4 subtype, to olfactory processing and behavior during the embryonic and adult stages.
Topics: Animals; Interneurons; Olfactory Bulb; Humans; Neurogenesis
PubMed: 38933598
DOI: 10.3389/fncir.2024.1427378 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2024Motor imagery is often used in the fields of sports training and neurorehabilitation for its advantages of being highly targeted, easy to learn, and requiring no special...
[A study on the effects of transcranial direct current stimulation combined with motor imagery on brain function based on electroencephalogram and near infrared spectrum].
Motor imagery is often used in the fields of sports training and neurorehabilitation for its advantages of being highly targeted, easy to learn, and requiring no special equipment, and has become a major research paradigm in cognitive neuroscience. Transcranial direct current stimulation (tDCS), an emerging neuromodulation technique, modulates cortical excitability, which in turn affects functions such as locomotion. However, it is unclear whether tDCS has a positive effect on motor imagery task states. In this paper, 16 young healthy subjects were included, and the electroencephalogram (EEG) signals and near-infrared spectrum (NIRS) signals of the subjects were collected when they were performing motor imagery tasks before and after receiving tDCS, and the changes in multiscale sample entropy (MSE) and haemoglobin concentration were calculated and analyzed during the different tasks. The results found that MSE of task-related brain regions increased, oxygenated haemoglobin concentration increased, and total haemoglobin concentration rose after tDCS stimulation, indicating that tDCS increased the activation of task-related brain regions and had a positive effect on motor imagery. This study may provide some reference value for the clinical study of tDCS combined with motor imagery.
Topics: Humans; Transcranial Direct Current Stimulation; Electroencephalography; Spectroscopy, Near-Infrared; Brain; Imagination; Motor Cortex; Hemoglobins; Young Adult
PubMed: 38932533
DOI: 10.7507/1001-5515.202310029 -
Clinical and Translational Science Jun 2024Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of...
Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1 miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1 and wild-type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1 miniswine demonstrated slower and shorter steps, indicative of a balance-preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1 miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.
Topics: Animals; Neurofibromatosis 1; Disease Models, Animal; Mice; Neurofibromin 1; Behavior, Animal; Male; Hippocampus; Cognitive Dysfunction; Oligodendroglia; Humans; Astrocytes; Female
PubMed: 38932491
DOI: 10.1111/cts.13858 -
Nutrients Jun 2024Taurine (2-aminoethanesulfonic acid) is a non-protein β-amino acid essential for cellular homeostasis, with antioxidant, anti-inflammatory, and cytoprotective...
Taurine (2-aminoethanesulfonic acid) is a non-protein β-amino acid essential for cellular homeostasis, with antioxidant, anti-inflammatory, and cytoprotective properties that are crucial for life maintenance. This study aimed to evaluate the effects of taurine administration on hippocampal neurogenesis, neuronal preservation, or reverse damage in rats exposed to forced ethanol consumption in an animal model. Wistar rats were treated with ethanol (EtOH) for a 28-day period (5% in the 1st week, 10% in the 2nd week, and 20% in the 3rd and 4th weeks). Two taurine treatment protocols (300 mg/kg i.p.) were implemented: one during ethanol consumption to analyze neuroprotection, and another after ethanol consumption to assess the reversal of ethanol-induced damage. Overall, the results demonstrated that taurine treatment was effective in protecting against deficits induced by ethanol consumption in the dentate gyrus. The EtOH+TAU group showed a significant increase in cell proliferation (145.8%) and cell survival (54.0%) compared to the EtOH+Sal group. The results also indicated similar effects regarding the reversal of ethanol-induced damage 28 days after the cessation of ethanol consumption. The EtOH+TAU group exhibited a significant increase (41.3%) in the number of DCX-immunoreactive cells compared to the EtOH+Sal group. However, this amino acid did not induce neurogenesis in the tissues of healthy rats, implying that its activity may be contingent upon post-injury stimuli.
Topics: Animals; Taurine; Neurogenesis; Rats, Wistar; Doublecortin Protein; Ethanol; Male; Neuroprotective Agents; Rats; Hippocampus; Cell Proliferation; Dentate Gyrus; Neurons; Cell Survival; Disease Models, Animal
PubMed: 38931326
DOI: 10.3390/nu16121973 -
Nutrients Jun 2024Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or...
Effects of Evodiamine on Behavior and Hippocampal Neurons through Inhibition of Angiotensin-Converting Enzyme and Modulation of the Renin Angiotensin Pathway in a Mouse Model of Post-Traumatic Stress Disorder.
Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or other catastrophic incidents, typically characterized by heightened anxiety, depressive symptoms, and cognitive dysfunction. In this study, animals subjected to single prolonged stress (SPS) were administered evodiamine (EVO) and compared to a positive control group receiving sertraline. The animals were then assessed for alterations in anxiety, depression, and cognitive function. Histological analysis was conducted to examine neuronal changes in the hippocampus. In order to predict the core targets and related mechanisms of evodiamine intervention in PTSD, network pharmacology was used. The metabolic markers pre- and post-drug administration were identified using nontargeted serum metabolomics techniques, and the intersecting Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened. Finally, the core targets were validated through molecular docking, enzyme-linked immunosorbent assays, and immunofluorescence staining to confirm the anti-PTSD effects and mechanisms of these targets. As well as improving cognitive impairment, evodiamine reversed anxiety- and depression-like behaviors. It also inhibited the reduction in the number of hippocampal neuronal cells and Nissl bodies in SPS mice inhibited angiotensin converting enzyme (ACE) levels in the hippocampus of SPS mice, and modulated the renin angiotensin pathway and its associated serum metabolites in brain tissue. Evodiamine shows promise as a potential candidate for alleviating the symptoms of post-traumatic stress disorder.
Topics: Animals; Stress Disorders, Post-Traumatic; Hippocampus; Quinazolines; Mice; Neurons; Disease Models, Animal; Male; Renin-Angiotensin System; Behavior, Animal; Angiotensin-Converting Enzyme Inhibitors; Depression; Molecular Docking Simulation; Anxiety; Mice, Inbred C57BL; Network Pharmacology
PubMed: 38931311
DOI: 10.3390/nu16121957 -
International Journal of Environmental... May 2024Ideational slippage-characterized by incorrect word usage and strained logic during dialogue-is common in aging and, at greater frequency, is an indicator of...
Ideational slippage-characterized by incorrect word usage and strained logic during dialogue-is common in aging and, at greater frequency, is an indicator of pre-clinical cognitive decline. Performance-based assessment of ideational slippage may be useful in the study of cognitive aging and Alzheimer's-disease-related pathology. In this preliminary study, we examine the association between corpus callosum volume and a performance-based assessment of ideational slippage in middle-aged and older adults (age 61-79 years). Ideational slippage was indexed from cognitive special scores using the Rorschach Inkblot Method (RIM), which are validated indices of deviant verbalization and logical inaccuracy (, ). Among middle-aged and older adults, smaller splenium volume was associated with greater ideational slippage (η = 0.48), independent of processing speed and fluid intelligence. The observed negative associations are consistent with visuospatial perception and cognitive functions of the splenium. The effect was strongest with the splenium, and volumes of the genu and total white matter had small effects that were not statistically significant. Conclusions: Results are discussed with future application of RIM special scores for the assessment of pre-clinical cognitive decline and, based on observed effect sizes, power analyses are reported to inform future study planning.
Topics: Humans; Middle Aged; Aged; Female; Male; Corpus Callosum; Cognition; Aging; Cognitive Dysfunction
PubMed: 38928903
DOI: 10.3390/ijerph21060656 -
International Journal of Molecular... Jun 2024In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the...
Combined Ionizing Radiation Exposure by Gamma Rays and Carbon-12 Nuclei Increases Neurotrophic Factor Content and Prevents Age-Associated Decreases in the Volume of the Sensorimotor Cortex in Rats.
In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.14 Gy carbon-12 nuclei) on the locomotor and exploratory activity of rats, and assessed the sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week and 7 months post-irradiation. The sensorimotor cortex tissues were processed to determine whether the behavioral and morphologic effects were associated with changes in neurotrophin content. The irradiated rats were characterized by increased locomotor and exploratory activity, as well as novelty-seeking behavior, at 3 days post-irradiation. At the same time, only unirradiated rats experienced a significant decrease in the sensorimotor cortex volume at 7 months. While there were no significant differences at 1 week, at 7 months, the irradiated rats were characterized by higher neurotrophin-3 and neurotrophin-4 content in the sensorimotor cortex. Thus, IR prevents the age-associated decrease in the sensorimotor cortex volume, which is associated with neurotrophic and neurogenic changes. Meanwhile, IR-induced increases in locomotor activity may be the cause of the observed changes.
Topics: Animals; Sensorimotor Cortex; Gamma Rays; Rats; Male; Nerve Growth Factors; Radiation, Ionizing; Neurotrophin 3; Aging; Locomotion; Magnetic Resonance Imaging
PubMed: 38928431
DOI: 10.3390/ijms25126725