Limbic System Research Papers - Academia.edu (original) (raw)

2025, Neuroscience Research

Neuropeptide B/W receptor 1 (NPBWR1) is a G-protein coupled receptor, which was initially reported as an orphan receptor, and whose ligands were identified by this and other groups in 2002 and 2003. To examine the physiological roles of NPBWR1, we examined phenotype of Npbwr1 2/2 mice. When presented with an intruder mouse, Npbwr1 2/2 mice showed impulsive contact with the strange mice, produced more intense approaches toward them, and had longer contact and chasing time along with greater and sustained elevation of heart rate and blood pressure compared to wild type mice. Npbwr1 2/2 mice also showed increased autonomic and neuroendocrine responses to physical stress, suggesting that impairment of NPBWR1 leads to stress vulnerability. We also observed that these mice show abnormality in the contextual fear conditioning test. These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses. Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses. These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

2025, Psychoneuroendocrinology

In view of the greater prevalence of depression and anxiety disorders in women than in men, functional magnetic resonance imaging (fMRI) studies have examined sex-differences in brain activations during emotion processing. Comparatively, sex-differences in brain connectivity received little attention, despite evidence for important fronto-limbic connections during emotion processing across sexes. Here, we investigated sex-differences in fronto-limbic connectivity during negative emotion processing. Forty-six healthy individuals (25 women, 21 men) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Sex steroid hormones and feminine-masculine traits were also measured. Subjective ratings of negative emotional images were higher in women than in men. Across sexes, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the right amygdala. Granger connectivity from right amygdala was significantly greater than that from dmPFC during the &amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;high negative&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; condition, an effect driven by men. Magnitude of this effect correlated negatively with highly negative image ratings and feminine traits and positively with testosterone levels. These results highlight critical sex differences in brain connectivity during negative emotion processing and point to the fact that both biological (sex steroid hormones) and psychosocial (gender role and identity) variables contribute to them. As the dmPFC is involved in social cognition and action planning, and the amygdala-in threat detection, the connectivity results suggest that compared to women, men have a more evaluative, rather than purely affective, brain response during negative emotion processing.

2025, Brain connectivity

Background: Major depressive disorder (MDD) is a mood disorder associated with disruptions in emotional control. Previous studies have investigated abnormal regional activity and connectivity within the fronto-limbic circuit. However, condition-specific connectivity changes and their association with the pathophysiology of MDD remain unexplored. This study investigated effective connectivity in the fronto-limbic circuit induced by negative emotional processing from patients with MDD. Methods: Thirty-four unmedicated female patients with MDD and 28 healthy participants underwent event-related functional magnetic resonance imaging at 7T while viewing emotionally negative and neutral images. Brain regions whose dynamics are driven by experimental conditions were identified by using statistical parametric mapping. Effective connectivity among regions of interest was then estimated by using dynamic causal modeling. Results: Patients with MDD had lower activation of the orbitofrontal cortex (OFC) and higher activation of the parahippocampal gyrus (PHG) than healthy controls (HC). In association with these regional changes, we found that patients with MDD did not have significant modulatory connections from the primary visual cortex (V1) to OFC, whereas those connections of HC were significantly positively modulated during negative emotional processing. Regarding the PHG activity, patients with MDD had greater modulatory connection from the V1, but reduced negative modulatory connection from the OFC, compared with healthy participants. Conclusions: These results imply that disrupted effective connectivity among regions of the OFC, PHG, and V1 may be closely associated with the impaired regulation of negative emotional processing in the female patients with MDD.

2025, Brain Connectivity

2025, Frontiers in Neural Circuits

Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP) and the medial prefrontal cortex (mPFC) in rats subjected to short term stress (STS) and chronic unpredictable stress (CUS). CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

2025, Archives of General Psychiatry

Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder of childhood. There is considerable evidence that brain dopamine is involved in ADHD, but it is unclear whether dopamine activity is enhanced or depressed. Objective: To test the hypotheses that striatal dopamine activity is depressed in ADHD and that this contributes to symptoms of inattention. Design: Clinical (ADHD adult) and comparison (healthy control) subjects were scanned with positron emission tomography and raclopride labeled with carbon 11 (D 2 /D 3 receptor radioligand sensitive to competition with endogenous dopamine) after placebo and after intravenous methylphenidate hydrochloride (stimulant that increases extracellular dopamine by blocking dopamine transporters). The difference in [ 11 C]raclopride's specific binding between placebo and methylphenidate was used as marker of dopamine release. Symptoms were quantified using the Conners Adult ADHD Rating Scales.

2025, JAMA

Context Loss of the capacity to experience pleasure (anhedonia) is a core clinical feature of schizophrenia. Although functional imaging techniques have been successful in identifying the neural basis of cognitive impairments in schizophrenia, no attempts to date have been made to investigate neural systems underlying emotional disturbances. Objective To study the neural basis of emotional processing in schizophrenia by exploring the pattern of brain responses to olfactory stimuli in patients and healthy volunteers.

2025, The Journal of Neuroscience

Neonatal, bilateral lesion of the ventral hippocampus (VH) in rats recently has been proposed as a model of schizophrenia because these animals show postpubertal hypersensitivity to stress and to dopamine (DA) agonists that can be reversed by neuroleptic treatment. In search of the mechanisms of postpubertal emergence of hyperdopaminergic behavior in this model, we investigated developmental expressions of DA D1, D2, and D3 receptors in various striatal and limbic subregions of rats that had received bilateral ibotenic acid lesion of the VH at postnatal day 7 (PD7). D-Amphetamine-, apomorphine-, and stress-induced changes in locomotor activity were measured and, in accordance with previous reports, we observed an increased locomotor activity at PD56 in the hippocampal-lesioned group. The expression of DA D1, D2, and D3 receptors was then estimated in these rats by ligand autoradiography at PD41 and PD62. We observed that the levels of DA D3 receptors, as measured by tritiated 7-hydr...

2025, Personality Disorders: Theory, Research, and Treatment

Although psychopathy has consistently been shown to distribute as a dimension, all prior studies have examined behavioral indicators that may be phenotypically distant from core biological correlates of the syndrome. The current studies attempted to determine whether biomarkers from a high-resolution structural magnetic resonance imaging (MRI) scan of selected limbic and paralimbic structures identified the latent structure of psychopathy as continuous. Participants were 254 adult male medium/maximum security inmates (Study 1) and 191 adolescent male maximum security inmates (Study 2) who volunteered to undergo research MRI scans. Indicators of gray matter concentration (GMC) in the adult sample and of gray matter volume (GMV) in the adolescent sample were subjected to taxometric analysis using three non-redundant taxometric procedures: mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent-mode factor analysis (L-Mode). Evidence of continuous latent structure was found across samples (adults, adolescents), measures (GMV, GMC, Psychopathy Checklist-Revised [PCL-R], Psychopathy Checklist: Youth Version [PCL: YV]) and procedures (MAMBAC, MAXCOV, L-Mode). Continuous latent structure was also noted when biomarker (GMV, GMC) and behavioral (PCL) indicators were included in the same analysis. The current results support the view that psychopathy is a quantitative construct on which people differ in degree ("more of" or "less of") rather than a qualitative construct that assigns people to distinct categories ("either or"). Continued development of the psychopathy construct may depend on our ability to identify, understand, and make effective use of its apparent continuous latent structure.

2025, Psychiatry Research: Neuroimaging

The basal ganglia are recognized as putative mediators of certain cognitive and behavioral symptoms of major depression. Moreover, patients with basal ganglia lesions have repeatedly exhibited significant affective symptomatology, including apathy, depressive mood, and psychosis. Using high resolution, axial T, intermediate magnetic resonance images, and a systematic sampling stereologic method, we assessed putamen nuclei volumes in 41 patients with major depression (DSM-III) and 44 healthy volunteer controls of similar age. Depressed patients had significantly smaller putamen nuclei compared with controls. Age was negatively correlated with putamen size in both groups. These results are the first demonstration of diminished putamen volumes in depression and further support a role for basal ganglia structures in the etiopathogenesis of depression.

2025, Network Neuroscience

Beyond the established effects of subthalamic nucleus deep brain stimulation (STN-DBS) in reducing motor symptoms in Parkinson’s disease, recent evidence has highlighted the effect on non-motor symptoms. However, the impact of STN-DBS on disseminated networks remains unclear. This study aimed to perform a quantitative evaluation of network-specific modulation induced by STN-DBS using Leading Eigenvector Dynamics Analysis (LEiDA). We calculated the occupancy of resting-state networks (RSNs) in functional MRI data from 10 patients with Parkinson’s disease implanted with STN-DBS and statistically compared between ON and OFF conditions. STN-DBS was found to specifically modulate the occupancy of networks overlapping with limbic RSNs. STN-DBS significantly increased the occupancy of an orbitofrontal limbic subsystem with respect to both DBS OFF (p = 0.0057) and 49 age-matched healthy controls (p = 0.0033). Occupancy of a diffuse limbic RSN was increased with STN-DBS OFF when compared wit...

2025, Neurology

Objective: To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age-and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods. In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Conclusions: Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity. Neurology â 2013;81:1417-1424 GLOSSARY ACC 5 anterior cingulate cortex; DMN 5 default mode network; GLM 5 general linear model; ICA 5 independent component analysis; MCS 5 minimally conscious state; PCC 5 posterior cingulate cortex; ROI 5 region of interest; VS 5 vegetative state; VTA 5 ventral tegmental area.

2025, Frontiers in Neural Circuits

2025

In the field of communication studies the preeminent forms of explanation of human behavior have been the social and psychological, but biological :origins may be as important to understanding human communication as are social origins. Communication research suggests a biological basis for certain patterns of adult interaction. Although these patterns of interaction do not exhaust all or even the most important aspects of huran interaction, there is ample evidence that they are functionay important to the adult and to the infant-adult relationship. The patterns of interaction may wen be the mechanism for defining caretaker-infant bonding. An appreciation of the intrica4.e relationship between social and biological behavior and the common biological bases of human communication is one result of looking for the biological sources of ultimate causation for patterns of human communication. The emphasis on learning, culture, and socialization, the emphasis on higher-level cognitive processes and on highly deliberate linguistic exchanges have had a central place in the study of human communication. But it is time to recognize that part of what makes communication human is its biological commonness across peoples and even species. (One hundred-and-two references are attached.) (RS)

2025, "Zenodo Repository"

The amygdala, a key structure in the limbic system of the human brain, is responsible for processing emotions such as fear, anger, and the need for survival. Throughout evolutionary history, this part of the brain has played an important role in maintaining human life, but today in modern societies, its constant presence in a state of alert and defense has led to consequences such as anxiety, unhealthy competition, and violence. This article examines the role of the amygdala with an interdisciplinary approach; from a scientific perspective, its function in the nervous system is examined; from a philosophical perspective, issues such as ownership, territory, and will are analyzed; and from a spiritual perspective, the possibility of humans freeing themselves from the dominance of fear and moving toward higher consciousness is analyzed. Finally, strategies are presented to balance the functioning of the amygdala and strengthen the prefrontal cortex so that humans can achieve peace, empathy, and self-knowledge.

2025, The Journal of neuroscience : the official journal of the Society for Neuroscience

Chronic pain attenuates midbrain dopamine (DA) transmission, as evidenced by a decrease in opioid-evoked DA release in the ventral striatum, suggesting that the occurrence of chronic pain impairs reward-related behaviors. However, mechanisms by which pain modifies DA transmission remain elusive. Using in vivo microdialysis and microinjection of drugs into the mesolimbic DA system, we demonstrate in mice and rats that microglial activation in the VTA compromises not only opioid-evoked release of DA, but also other DA-stimulating drugs, such as cocaine. Our data show that loss of stimulated extracellular DA is due to impaired chloride homeostasis in midbrain GABAergic interneurons. Treatment with minocycline or interfering with BDNF signaling restored chloride transport within these neurons and recovered DA-dependent reward behavior. Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic sign...

2025, Neuro endocrinology letters

The goal of the study was an evaluation of differences in working memory effectiveness between patients with type 1 and type 2DM. It was also attempted to ascertain whether the level of diabetes control is associated with working memory effectiveness. 62 subjects were enrolled into the study. All patients were divided into two groups: patients with type 1DM (n=31) and with type 2DM (n=31). The Trail Making Test (TMT) and the Stroop Test were used for evaluation of working memory effectiveness. Diabetes control indicators included: glycated haemoglobin (HbA1C) level, total cholesterol concentration, HDL and LDL cholesterol concentration and body mass index (BMI). The patients with type 1DM obtained a significantly lower time in the execution of TMT, part B (p=0.01) and of RCNb (p=0.01) and NCWd (p=0.01) versions of the Stroop Test, while making significantly less errors in NCWd version (p=0.01). Significant correlations were demonstrated between BMI values and the rate of execution o...

2025, Annals of neurology

To determine whether the frequency of TDP-43 deposition in Alzheimer's disease (AD) differs across pathologically defined AD subtypes (Hippocampal sparing [HpSp]; Typical and Limbic), and to further examine the relationship between TDP-43, pathological subtype, and clinical features in AD. We identified all cases with pathologically-confirmed AD (NIA-Reagan intermediate-high probability, Braak stage IV-VI) independent of cognitive status (n=188). Neurofibrillary tangle counts were performed using thioflavin-S microscopy in hippocampus and three neocortical regions, and all cases were subtyped: HpSp AD Pathology (n=19); Typical AD Pathology (n=136); Limbic AD Pathology (n=33). TDP-43 immunoreactivity was performed in multiple brain regions to assess for the presence of TDP-43 and TDP-43 stage. All cases were clinically sub-classified at presentation as Amnestic AD Dementia versus Atypical AD Dementia. Statistical analysis was performed using linear and penalized logistic regressi...

2025, Journal of Neuroscience Research

The midbrain central gray (periaqueductal gray; PAG) mediates defensive behaviors and is implicated in the rewarding effects of opiate drugs. Projections from the PAG to the ventral tegmental area (VTA) suggest that this region might also regulate behaviors involving motivation and cognition. However, studies have not yet examined the morphological features of PAG axons in the VTA or whether they synapse onto dopamine (DA) or GABA neurons. In this study, we injected anterograde tracers into the rat PAG and used immunoperoxidase to visualize the projections to the VTA. Immunogold-silver labeling for tyrosine hydroxylase (TH) or GABA was then used to identify the phenotype of innervated cells. Electron microscopic examination of the VTA revealed axons labeled anterogradely from the PAG, including myelinated and unmyelinated fibers and axon varicosities, some of which formed identifiable synapses. Approximately 55% of these synaptic contacts were of the symmetric (presumably inhibitory) type; the rest were asymmetric (presumably excitatory). These findings are consistent with the presence of both GABA and glutamate projection neurons in the PAG. Some PAG axons contained dense-cored vesicles indicating the presence of neuropeptides in addition to classical neurotransmitters. PAG projections synapsed onto both DA and GABA cells with no obvious selectivity, providing the first anatomical evidence for these direct connections. The results suggest a diverse nature of PAG physiological actions on midbrain neurons. Moreover, as both the VTA and PAG are implicated in the reinforcing actions of opiates, our findings provide a potential substrate for some of the rewarding effects of these drugs.

2025

Background: The occipital cortex is positioned on the back of the brain, and it is responsible for processing visual information. Ketamine is a drug used as an anesthetic. Common anesthetics can cause neurotoxicity, with the occipital cortex being one of the most vulnerable areas. Aim: To estimate the histological alteration in the occipital cortices of newborn mice receiving ketamine injections at therapeutic doses during pregnancy. Methodology: This study involved 30 pregnant female mice (8-12 weeks old), who are split into two groups: the experimental group, given 50 mg/kg ketamine hydrochloride intraperitoneally, and the control group, given distal water intraperitoneally. The mice were then subjected to a paraffin wax embedding procedure, and their neural tissue was examined using a Cresyl violet stain. The results were analyzed using the Spss software and the independent t-test. Results: Significant variability was seen when the number of cells in the mice's occipital cerebral cortex after ketamine injection during pregnancy was compared. In the control group, the difference between the mean of the superficial layer and the deep layer is 85.4%, while in the experimental group, the difference between the two layers is 85.1%. In this study, there was significant variability in the number of cells between the control groups (Mean ± SD) is 1326±14.4 cells and the experimental group (Mean ± SD) is798.06 ±26.9 cells in the occipital cortex. In calculation, the experimental newborn mice's occipital cortex showed apoptotic alterations following a ketamine injection during pregnancy. Conclusion: The experimental newborn mice's occipital cortex showed apoptotic alterations following a ketamine injection during pregnancy. These results are in line with growing concerns regarding the neurotoxic effects of anesthetic drugs on the developing brain.

2025, Behavioural Brain Research

Immunohistochemical Fos staining has proven to be a method to identify the neurons that are activated by stimulation. Although methamphetamine (MA)-conditioned place preference (CPP) memory was longlasting, how this memory was established and retrieved remained unknown. We used the vehicle-and MA-conditioned environment (including cues and context) to reactivate the MA-CPP memory in mice. In the limbic system, Fos-positive neurons were examined following retrieval of the MA-CPP memory. We demonstrated that the current conditioning procedure produced reliable MA-CPP performance. Moreover, enhanced Fos expressions were found in the medial prefrontal cortex and the core of the nucleus accumbens after reactivation of the MA-CPP memory. Furthermore, familiarity with the environmental cues/context was found to significantly enhance Fos expressions in dorsal striatum and dentate gyrus. Nucleus accumbens shell, basolateral or lateral amygdala, in this regard, did not seem to be involved in retrieval of the MA-CPP memory. These results, taken together, suggest that the medial prefrontal cortex and the core of the nucleus accumbens are anatomical substrates responsible for reactivation of the MA-CPP memory.

2025, PLOS ONE

Background. Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. Methodology/Principal Findings. Using functional magnetic resonance imaging (fMRI), we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC) and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. Conclusions. These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression.

2025, PloS one

Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses.

2025, The Journal of Neuroscience

Editor's Note: These short reviews of a recent paper in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to mimic the journal clubs that exist in your own departments or institutions. For more... more

2025, PLOS ONE

While the limbic system theory continues to be part of common scientific parlance, its validity has been questioned on multiple grounds. Nonetheless, the issue of whether or not there exists a set of brain areas preferentially dedicated to emotional processing remains central within affective neuroscience. Recently, a widespread neural reference space for emotion which includes limbic as well as other regions was characterized in a large meta-analysis. As methodologically heterogeneous studies go into such meta-analyses, showing in an individual study in which all parameters are kept constant, the involvement of overlapping areas for various emotion conditions in keeping with the neural reference space for emotion, would serve as valuable confirmatory evidence. Here, using fMRI, 20 young adult men were scanned while viewing validated neutral and effective emotion-eliciting short film excerpts shown to quickly and specifically elicit disgust, amusement, or sexual arousal. Each emotion-specific run included, in random order, multiple neutral and emotion condition blocks. A stringent conjunction analysis revealed a large overlap across emotion conditions that fit remarkably well with the neural reference space for emotion. This overlap included symmetrical bilateral activation of the medial prefrontal cortex, the anterior cingulate, the temporo-occipital junction, the basal ganglia, the brainstem, the amygdala, the hippocampus, the thalamus, the subthalamic nucleus, the posterior hypothalamus, the cerebellum, as well as the frontal operculum extending towards the anterior insula. This study clearly confirms for the visual modality, that processing emotional stimuli leads to widespread increases in activation that cluster within relatively confined areas, regardless of valence.

2025, Neuroscience

In£ammatory cytokines are rapidly induced in glia by epileptic activity. We show that pentraxin 3 immunoreactivity and mRNA are enhanced in the rat forebrain above undetectable control levels by limbic seizures with a dual pattern of induction. Within 6 h from seizure onset, pentraxin 3 immunoreactivity was increased in astrocytes. Eighteen to 48 h later, speci¢c neuronal populations and leucocytes were strongly immunoreactive only in areas of neurodegeneration. This staining was abolished when neuronal cell loss, but not seizures, was prevented by blocking N-methyl-D-aspartate receptors. Pentraxin 3 3/3 mice had a more widespread seizure-related neuronal damage in the forebrain than their wild-type littermates although both groups had similar epileptic activity. Our results provide evidence that pentraxin 3 is synthesized in brain after seizures and may exert a protective role in seizure-induced neurodegeneration.

2025, Cerebral Cortex

Decision-making involves frontolimbic and dopaminergic brain regions, but how prior choice outcomes, dopamine neurotransmission, and frontostriatal activity are integrated to affect choices is unclear. We tested 60 healthy volunteers using the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging. In the BART, participants can pump virtual balloons to increase potential monetary reward or cash out to receive accumulated reward; each pump presents greater risk and potential reward (represented by the pump number). In a separate session, we measured striatal D2/D3 dopamine receptor binding potential (BP ND ) with positron emission tomography in 13 of the participants. Losses were followed by fewer risky choices than wins; and during risk-taking after loss, amygdala and hippocampal activation exhibited greater modulation by pump number than after a cash-out event. Striatal D2/D3 BP ND was positively related to the modulation of ventral striatal activation when participants decided to cash out and negatively to the number of pumps in the subsequent trial; but negatively related to the modulation of prefrontal cortical activation by pump number when participants took risk, and to overall earnings. These findings provide in vivo evidence for a potential mechanism by which dopaminergic neurotransmission may modulate risk-taking behavior through an interactive system of frontal and striatal activity.

2025, The Journal of Comparative Neurology

Olfactory bulb development in mouse embryos from day 10 of gestation (E10) to E l 5 was studied with 1 p plastic sections and Golgi impregnations. Olfactory nerve axons reach the presumptive olfactory bulb region of the cerebral vesicle at E12, the same time that the first young neurons (postmitotic neuroblasts) are seen in the newly-formed intermediate (mantle) layer. By E l 4 many of the presumptive mitral cells are oriented tangential to the surface and have grown a long axon that enters the lateral olfactory tract on the surface of the presumptive piriform cortex. The following probable sequence of differentiation of mitral cells was determined from Golgi impregnations of El4 and E l 5 animals: ( 1 ) After regrowth of an internal and external process following rounding up at mitosis, the nucleus and perikaryon of certain ventricular cells migrate into the deepest portion of the intermediate layer and start to re-orient into a tangential orientation. This stage is called the primitive radial stage. ( 2 ) The growth of tangential processes combined with withdrawal or atrophy of external and internal primitive radial processes follows to produce cells in the pre-axonic tangential stage. ( 3 ) The tangential cells then acquire a long, thin, unbranched process (axon) oriented towards the lateral olfactory tract and a larger, branching process (dendrite) running in the opposite direction. This stage is called the tangential mitral cell stage. (4) Radial re-orientation of the perikaryon and dendrites of these cells and external migration of the perikaryon results in cells in the radial mitral cell stage.

2025, Journal of Comparative Neurology

Cell proliferation and migration in the developing mouse olfactory bulb was studied by autoradiography. Animals were injected with thymidine‐H3 at various developmental stages and killed one to 96 hours later. All neurons arise in the germinal zone surrounding the ventricle. Until the fourteenth day of gestation (E14) this zone consists only of a matrix (primitive ependymal) layer. From E14 to E17 both matrix and subependymal layers are found, and from E18 to maturity only the subependymal layer is present. The matrix layer produces the mitral cells and some tufted and granule cells; the subependymal layer gives origin to some tufted cells and most of the granule cells. Mitral cell neuroblasts migrate peripherally to reach the primitive mitral cell layer three days after final DNA synthesis. Tufted cell neuroblasts migrate through the developing mitral cell layer to reach their definitive locations; external granule cell neuroblasts migrate past both developing mitral and tufted cel...

2025

Premio extraordinario de Trabajo Fin de Master curso 2013-2014. Ingles para la cualificacion profesional

2025, Hormones and Behavior

Central administration of oxytocin (OT) antagonists inhibits maternal and sexual behavior in nonprimates, providing the strongest experimental evidence that endogenous OT facilitates these behaviors. While there have been a few reports that ICV administration of OT increases social behaviors in monkeys, no studies to date have assessed the effects of OT antagonists. Therefore, we studied in rhesus monkeys whether L368,899®, a non-peptide antagonist produced by Merck that selectively blocks the human uterine OT receptor, penetrates the CNS after peripheral administration and alters female maternal and sexual behavior. In two studies in four male monkeys, L368,899 was injected iv (1 mg/kg) after which (1) CSF samples were collected at intervals over 4 h and (2) brains were collected at 60 min. Assay of samples confirmed that iv-administered L368,899 entered CSF and accumulated in the hypothalamus, septum, orbitofrontal cortex, amygdala and hippocampus, but not other areas. An adult female monkey was tested for interest in either an infant or sexual behavior, receiving a different iv treatment prior to each test (1 or 3 mg/kg of L368,899 or saline) OT antagonist treatment reduced or eliminated interest in the infant and sexual behavior. These results, although preliminary, are the first to directly implicate endogenous OT in activation of primate maternal interest and sexual behavior. While it remains to be empirically demonstrated that peripherally administered L368,899 blocks central OT receptors, our behavioral findings suggest that this nonpeptide antagonist may facilitate testing OT involvement in a variety of social and other behaviors in primates.

2025, Hormones and Behavior

2025, The Journal of Neuroscience

Neural correlates of responses to emotionally valenced olfactory, visual, and auditory stimuli were examined using positron emission tomography. Twelve volunteers were scanned using the water bolus method. For each sensory modality, regional cerebral blood flow (rCBF) during presentation of both pleasant and unpleasant stimuli was compared with that measured during presentation of neutral stimuli. During the emotionally valenced conditions, subjects performed forced-choice pleasant and unpleasant judgments. During the neutral conditions, subjects were asked to select at random one of a two key-press buttons. All stimulations were synchronized with inspiration, using an airflow olfactometer, to present the same number of stimuli for each sensory modality. A no-stimulation control condition was also performed in which no stimulus was presented. For all three sensory modalities, emotionally valenced stimuli led to increased rCBF in the orbitofrontal cortex, the temporal pole, and the superior frontal gyrus, in the left hemisphere. Emotionally valenced olfactory and visual but not auditory stimuli produced additional rCBF increases in the hypothalamus and the subcallosal gyrus. Only emotionally valenced olfactory stimuli induced bilateral rCBF increases in the amygdala. These findings suggest that pleasant and unpleasant emotional judgments recruit the same core network in the left hemisphere, regardless of the sensory modality. This core network is activated in addition to a number of circuits that are specific to individual sensory modalities. Finally, the data suggest a superior potency of emotionally valenced olfactory over visual and auditory stimuli in activating the amygdala.

2025

This paper reports the results of a study on the effect of playing the guitar has on physical and mental wellness

2025, PubMed

Background: Maternal deprivation (MD) in rodents is an important neurodevelopmental model for studying a variety of behavioral changes which closely resemble the symptoms of schizophrenia in humans. Subjects and methods: To determine whether early-life stress leads to changes in the limbic system structures: the amygdala and the nucleus accumbens, 9-day-old Wistar rats were exposed to 24 hour MD. On P60 the rats were sacrificed for morphometric analysis and their brains were compared to the control group. Results: Results show that MD affected important limbic system structures: the amygdala and the nucleus accumbens, whose volume was decreased (17% of the control value for the amygdala and 9% of the control value for the nucleus accumbens ), as well as the number of neurons (41% of the control value for the amygdala and 43% of the control value for the nucleus accumbens ) and the size of their cells soma (12% of the control value for the amygdala and 33% of the control value for the nucleus accumbens ). Conclusion: This study indicates that early stress in life leads to changes in the morphology of the limbic areas of the brain, most probably due to the loss of neurons during postnatal development, and it further contributes to our understanding of the effects of maternal deprivation on brain development.

2025, Pediatric dentistry

Dental publications on autism have been sparse since the first comprehensive article geared for the dental profession. New findings on the etiology of autistic disorder (AD) have been discovered, suggesting that it is an organic disorder characterized by abnormalities in the brain, especially the cerebellum and limbic system. This article summarizes the latest medical findings on the etiology, diagnosis, and treatment approaches of AD, and reviews the dental literature since 1969. The main dental topics reviewed are: oral health status and dental needs of patients with AD, characteristics of patients with AD, and self-injurious behavior (SIB) in the context of AD. Clinical behavior-management issues such as pharmacological and communicative techniques and physical restraint and desensitization are described. The affect of the dental office's environment and appointment structure on a patient with AD are presented.

2025, Environmental Health Insights

Effects of dioxins on cognitive functions were reported in previous studies conducted in humans and animals. In the present study, we investigated the influence of dioxin exposure during pregnancy on social interaction and on the activity of offspring, which are related to neurodevelopmental disturbances. In addition, we analyzed neurochemical alterations of the limbic system of rat brains to suggest one mechanism of dioxin effects on brain function. We believe that this manuscript is suitable for publication in “Environmental Health Insights” because it provides an interesting topic for a wide global audience.To clarify the relationships between maternal dioxin exposure and socioemotional functions of rat offspring, dams were given TCDD (1.0 μg/kg) on gestational day 15. Social interactions and forced swimming time were compared between TCDD-exposed and control offspring in each gender. Frequency and duration of locomotion were higher, and durations per one behavior of proximity an...

2025, British Journal of Psychiatry

2025, Cortex

The concept of a (single) limbic system is shown to be outmoded. Instead, anatomical, neurophysiological, functional neuroimaging, and neuropsychological evidence is described that anterior limbic and related structures including the orbitofrontal cortex and amygdala are involved in emotion, reward valuation, and reward-related decisionmaking (but not memory), with the value representations transmitted to the anterior cingulate cortex for actioneoutcome learning. In this 'emotion limbic system' a computational principle is that feedforward pattern association networks learn associations from visual, olfactory and auditory stimuli, to primary reinforcers such as taste, touch, and pain. In primates including humans this learning can be very rapid and rule-based, with the orbitofrontal cortex overshadowing the amygdala in this learning important for social and emotional behaviour. Complementary evidence is described showing that the hippocampus and limbic structures to which it is connected including the posterior cingulate cortex and the fornix-mammillary body-anterior thalamus-posterior cingulate circuit are involved in episodic or event memory, but not emotion. This 'hippocampal system' receives information from neocortical areas about spatial location, and objects, and can rapidly associate this information together by the different computational principle of autoassociation in the CA3 region of the hippocampus involving feedback. The system can later recall the whole of this information in the CA3 region from any component, a feedback process, and can recall the information back to neocortical areas, again a feedback (to neocortex) recall process. Emotion can enter this memory system from the orbitofrontal cortex etc., and be recalled back to the orbitofrontal cortex etc. during memory recall, but the emotional and hippocampal networks or 'limbic systems' operate by different computational principles, and operate independently of each other except insofar as an emotional state or reward value attribute may be part of an episodic memory.

2025, The Journal of Neuroscience

Chronic exposure to opiates produces dependence and addiction, which may result from neuroadaptations in the dopaminergic reward pathway and its target brain regions. The neuronal protein α-synuclein has been implicated in neuronal plasticity and proposed to serve as a negative regulator of dopamine neurotransmission. Thus, α-synuclein could mediate some effects of opiates in the brain. The present study investigated the influence of acute and chronic morphine administration on α-synuclein mRNA and protein expression in the brains of mice. Downregulation of α-synuclein mRNA was observed in the basolateral amygdala, dorsal striatum, nucleus accumbens, and ventral tegmental area of mice withdrawn from chronic morphine treatment. The changes were the most pronounced after longer periods of withdrawal (48 h). In contrast, levels of α-synuclein protein, as assessed by Western blotting, were significantly increased in the amygdala and striatum/accumbens (but not in the mesencephalon) of m...

2025, Neuron

A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos-based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit.

2025

Background: Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype. Methods: Male CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec). Results: DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies. Conclusions: Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro-behavioural alterations, coming along with an experimentally-induced rise of circulating DAT-directed aAbs, open the issue of a potential role for auto-immunity in vulnerability to impulse-control disorders.

2025, Proceedings of the National Academy of Sciences

Humans often sacrifice material benefits to endorse or to oppose societal causes based on moral beliefs. Charitable donation behavior, which has been the target of recent experimental economics studies, is an outstanding contemporary manifestation of this ability. Yet the neural bases of this unique aspect of human altruism, which extends beyond interpersonal interactions, remain obscure. In this article, we use functional magnetic resonance imaging while participants anonymously donated to or opposed real charitable organizations related to major societal causes. We show that the mesolimbic reward system is engaged by donations in the same way as when monetary rewards are obtained. Furthermore, medial orbitofrontal–subgenual and lateral orbitofrontal areas, which also play key roles in more primitive mechanisms of social attachment and aversion, specifically mediate decisions to donate or to oppose societal causes. Remarkably, more anterior sectors of the prefrontal cortex are dist...

2025, Neuroscience Letters

The aim of a present study was to analyse the gene expression profiles in the periaqueductal grey (PAG) of rats related to their exploratory activity in the elevated plus-maze model of anxiety. Animals were divided into the groups according to their exploratory activity in the plusmaze as follows: rats with low activity ('anxious'), moderate activity ('intermediate') and high activity ('non-anxious'). Control animals were not exposed to the elevated plus-maze. The differential expression of genes was analysed using the cDNA representational difference analysis (RDA) in combination with the sequencing and database search. Reverse transcription-polymerase chain reaction with specific primers was applied to confirm the differences found by the RDA. We established that animals displaying the different exploratory activity have also the different gene expression profiles in the PAG. Among the identified genes, we were able to confirm the increased expression of limbic system-associated membrane protein (LSAMP) in animals having the reduced exploratory activity in the elevated plus-maze. 'Anxious' group of rats had 1.6-fold higher expression of LSAMP gene compared to 'non-anxious' animals. By contrast, 'home-cage' control rats and 'intermediate' group did not differ significantly by their LSAMP gene expression level. In conclusion, it is likely that LSAMP plays a role in the regulation of exploratory behaviour of rats in the novel aversive environment.

2025, Proceedings of the National Academy of Sciences

DTNBP1 (dystrobrevin binding protein 1) is a leading candidate susceptibility gene in schizophrenia and is associated with working memory capacity in normal subjects. In schizophrenia, the encoded protein dystrobrevin-binding protein 1 (dysbindin-1) is often reduced in excitatory cortical limbic synapses. We found that reduced dysbindin-1 in mice yielded deficits in auditory-evoked response adaptation, prepulse inhibition of startle, and evoked γ-activity, similar to patterns in schizophrenia. In contrast to the role of dysbindin-1 in glutamatergic transmission, γ-band abnormalities in schizophrenia are most often attributed to disrupted inhibition and reductions in parvalbumin-positive interneuron (PV cell) activity. To determine the mechanism underlying electrophysiological deficits related to reduced dysbindin-1 and the potential role of PV cells, we examined PV cell immunoreactivity and measured changes in net circuit activity using voltage-sensitive dye imaging. The dominant ci...

2025, American Journal of Psychiatry

Objective-Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. Here we used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Methods-fMRI (3T) BOLD response was examined in 21 controls and 16 patients during a two-choice recognition task using images of human faces. Each target face had previously been displayed with a threatening or non-threatening affect, but here were displayed with neutral affect. Responses to successful recognition and for the effect of previously threatening vs. nonthreatening affect were evaluated, and correlations with total BPRS examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Results-Patients performed the task more slowly than controls. Controls recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Controls exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed a weakening of that relationship. Conclusions-Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between two brain systems often examined in isolation. This finding suggests that abnormal

2025, Brain Network Disorders

Background: Synchronization across neural circuits is inextricably associated with brain function and pathology. Although not largely explored, this framework can be applied to baseline anxiety and its disorder, which is characterized by aberrant levels of synchronization between the amygdala nuclei and other areas of the extended amygdala, particularly the bed nucleus of the stria terminalis (BNST) and those outside this complex. Here, we aimed to test the hypothesis that a temporally complex form of electrical stimulation (non-periodic stimulation [NPS]) of the amygdala, specifically designed to disrupt hypersynchronous activity in epilepsy, a major comorbidity of pathological anxiety, may reduce its symptoms. Methods: Wistar rats were subjected to a physical restriction protocol model of stress to induce pathological anxiety and were assessed using the gold standard elevated plus maze (EPM) and open field (OF) tests. Result: In all criteria measured by the tests, NPS animals displayed reduced levels of anxiety-related symptoms, back at physiological levels. Conclusions: Considering the known effects and mechanisms of NPS on epileptic phenomena, we hypothesized that the therapeutic effects were achieved by desynchronization (or normalization of synchronism levels) across brain circuits involving the amygdala, BNST, and others. Overall, past and present findings suggest that NPS may be considered as a therapeutic alternative for the treatment of anxiety disorders.

2025, Cell and Tissue Research

On the one hand, the emotional state can influence food intake and on the other hand, hunger can have an impact on the emotional state. Leptin, which is encoded by the ob gene, is involved in the energy homeostasis and plays a role in development of obesity. Mice deficient for leptin (ob/ob) are obese and display several behavioral alterations. It has been shown that ob/ob mice display striking changes in neuronal plasticity within the limbic system, e.g., hippocampal formation. We focus on alterations in ob/ob mice that can be related to alter processing in another part of the limbic system, the amygdala. ob/ob mice have a higher food consumption than age-matched controls, which might have an impact on the emotional state of these mice. Since the amygdala is involved in emotional processing, we analyze whether ob/ob mice display alterations in plasticity at the electrophysiological and structural level. No changes were seen in dendritic spine densities in the basolateral and lateral (LA) nucleus of the amygdala. Interestingly and in contrast to the hippocampus , long-term potentiation in the LA was increased in ob/ob mice. Our results indicate that amygdalar and hippocampal synaptic plasticity are regulated in different ways by leptin deficiency in accordance with the different functions of these limbic structures in stress and anxiety.