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Brain Structure & Function Dec 2019Evidence is provided for a new conceptualization of the connectivity and functions of the cingulate cortex in emotion, action, and memory. The anterior cingulate cortex... (Review)
Review
Evidence is provided for a new conceptualization of the connectivity and functions of the cingulate cortex in emotion, action, and memory. The anterior cingulate cortex receives information from the orbitofrontal cortex about reward and non-reward outcomes. The posterior cingulate cortex receives spatial and action-related information from parietal cortical areas. It is argued that these inputs allow the cingulate cortex to perform action-outcome learning, with outputs from the midcingulate motor area to premotor areas. In addition, because the anterior cingulate cortex connects rewards to actions, it is involved in emotion; and because the posterior cingulate cortex has outputs to the hippocampal system, it is involved in memory. These apparently multiple different functions of the cingulate cortex are related to the place of this proisocortical limbic region in brain connectivity.
Topics: Animals; Emotions; Gyrus Cinguli; Humans; Limbic System; Memory; Motor Activity; Neural Pathways; Reward
PubMed: 31451898
DOI: 10.1007/s00429-019-01945-2 -
The American Journal of Psychiatry May 2020The search for more effective treatments for depression is a long-standing primary objective in both psychiatry and translational neuroscience. From initial models... (Review)
Review
The search for more effective treatments for depression is a long-standing primary objective in both psychiatry and translational neuroscience. From initial models centered on neurochemical deficits, such as the monoamine hypothesis, research toward this goal has shifted toward a focus on network and circuit models to explain how key nodes in the limbic system and beyond interact to produce persistent shifts in affective states. To build these models, researchers have turned to two complementary approaches: neuroimaging studies in human patients (and their healthy counterparts) and neurophysiology studies in animal models, facilitated in large part by optogenetic and chemogenetic techniques. As the authors discuss, functional neuroimaging studies in humans have included largely task-oriented experiments, which have identified brain regions differentially activated during processing of affective stimuli, and resting-state functional MRI experiments, which have identified brain-wide networks altered in depressive states. Future work in this area will build on a multisite approach, assembling large data sets across diverse populations, and will also leverage the statistical power afforded by longitudinal imaging studies in patient samples. Translational studies in rodents have used optogenetic and chemogenetic tools to identify not just nodes but also connections within the networks of the limbic system that are both critical and permissive for the expression of motivated behavior and affective phenotypes. Future studies in this area will exploit mesoscale imaging and multisite electrophysiology recordings to construct network models with cell-type specificity and high statistical power, identifying candidate circuit and molecular pathways for therapeutic intervention.
Topics: Animals; Depressive Disorder; Disease Models, Animal; Forecasting; Humans; Limbic System; Longitudinal Studies; Magnetic Resonance Imaging; Nerve Net; Neural Pathways
PubMed: 32354265
DOI: 10.1176/appi.ajp.2020.20030280 -
F1000Research 2020Fear is a response to impending threat that prepares a subject to make appropriate defensive responses, whether to freeze, fight, or flee to safety. The neural circuits... (Review)
Review
Fear is a response to impending threat that prepares a subject to make appropriate defensive responses, whether to freeze, fight, or flee to safety. The neural circuits that underpin how subjects learn about cues that signal threat, and make defensive responses, have been studied using Pavlovian fear conditioning in laboratory rodents as well as humans. These studies have established the amygdala as a key player in the circuits that process fear and led to a model where fear learning results from long-term potentiation of inputs that convey information about the conditioned stimulus to the amygdala. In this review, we describe the circuits in the basolateral amygdala that mediate fear learning and its expression as the conditioned response. We argue that while the evidence linking synaptic plasticity in the basolateral amygdala to fear learning is strong, there is still no mechanism that fully explains the changes that underpin fear conditioning.
Topics: Amygdala; Basolateral Nuclear Complex; Fear; Humans; Long-Term Potentiation; Neuronal Plasticity
PubMed: 32047613
DOI: 10.12688/f1000research.21201.1 -
Neuropsychopharmacologia Hungarica : a... Sep 2020The incidence of borderline personality disorder (BPD) in psychiatric care has shown growing tendencies. Despite its frequency, it is an underdiagnosed disease. Profound... (Review)
Review
The incidence of borderline personality disorder (BPD) in psychiatric care has shown growing tendencies. Despite its frequency, it is an underdiagnosed disease. Profound knowledge of etiological factors of BPD is essential for the proper diagnosis and treatment. The present study aims to provide a developmental psychopathological analysis of borderline personality disorder, which includes a thorough review of genetic and environmental etiological factors, an introduction to the functionalist approach of evolutionary perspective, and an overview of age specific characteristics of borderline symptoms. Recent research suggests that in addition to neurobiological and psychosocial factors, genetic vulnerability may be responsible for the development of BPD. Psychosocial background includes childhood trauma, maternal mental illness, maladaptive parenting styles and dysfunctional parent-child relationship, all of which are recognized as contributing factors to the development of insecure or disorganized attachment styles in the infant. Regarding the neurobiological background, changes in the hypothalamic-pituitary-adrenal axis, neurotransmission, endogenous opioid system, and neuroplasticity play a prominent role, the development of which is also affected by childhood traumatic events. Brain imaging studies reveal differences in the limbic system (hippocampus, amygdala) and frontal cortex, which are also involved in stress response, cognition, memory function, and emotion regulation. Early developmental processes may also play an important role in the development of the disorder, as depression during pregnancy or increased stress affects the quality of maternal care and may also affect gene expression through epigenetic mechanisms. With respect to the gene-environment interaction, the interaction of the child's impulsive traits and the invalidating family environment can be highlighted, which can lead to disruption of emotion regulation. The persistence of BPD symptoms is supported by the evolutionary approach concerning several aspects. Fear of abandonment can be explained by the anticipation of exclusion and maladaptive attempts to avoid it. Developmental psychopathological analysis contributes to the development of effective prevention and intervention tools through a better understanding of the background of borderline personality disorder. In terms of prognosis, as a result of effective treatments, symptoms can be reduced, so improvement can be achieved in a large proportion of patients.
Topics: Borderline Personality Disorder; Female; Humans; Hypothalamo-Hypophyseal System; Impulsive Behavior; Pituitary-Adrenal System; Pregnancy; Psychopathology
PubMed: 33055291
DOI: No ID Found -
Nature Neuroscience Jun 2021Social interactions and relationships are often rewarding, but the neural mechanisms through which social interaction drives positive experience remain poorly...
Social interactions and relationships are often rewarding, but the neural mechanisms through which social interaction drives positive experience remain poorly understood. In this study, we developed an automated operant conditioning system to measure social reward in mice and found that adult mice of both sexes display robust reinforcement of social interaction. Through cell-type-specific manipulations, we identified a crucial role for GABAergic neurons in the medial amygdala (MeA) in promoting the positive reinforcement of social interaction. Moreover, MeA GABAergic neurons mediate social reinforcement behavior through their projections to the medial preoptic area (MPOA) and promote dopamine release in the nucleus accumbens. Finally, activation of this MeA-to-MPOA circuit can robustly overcome avoidance behavior. Together, these findings establish the MeA as a key node for regulating social reward in both sexes, providing new insights into the regulation of social reward beyond the classic mesolimbic reward system.
Topics: Amygdala; Animals; Conditioning, Operant; Female; Hypothalamus; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Optogenetics; Reinforcement, Psychology; Reward; Social Behavior
PubMed: 33820999
DOI: 10.1038/s41593-021-00828-2 -
Brain Topography May 2023The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex,... (Review)
Review
The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity of the limbic circuits based on the published literature as an update to the original Papez circuit.
Topics: Humans; Limbic System; Gyrus Cinguli; Amygdala; Thalamus; Hippocampus; Neural Pathways
PubMed: 37148369
DOI: 10.1007/s10548-023-00955-y -
Nature Reviews. Neuroscience Aug 2023There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this... (Review)
Review
There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.
Topics: Animals; Humans; Dentate Gyrus; Hippocampus; Mental Recall; Learning; Mammals
PubMed: 37316588
DOI: 10.1038/s41583-023-00710-z -
Science (New York, N.Y.) Dec 2022Learning to predict rewards based on environmental cues is essential for survival. It is believed that animals learn to predict rewards by updating predictions whenever...
Learning to predict rewards based on environmental cues is essential for survival. It is believed that animals learn to predict rewards by updating predictions whenever the outcome deviates from expectations, and that such reward prediction errors (RPEs) are signaled by the mesolimbic dopamine system-a key controller of learning. However, instead of learning prospective predictions from RPEs, animals can infer predictions by learning the retrospective cause of rewards. Hence, whether mesolimbic dopamine instead conveys a causal associative signal that sometimes resembles RPE remains unknown. We developed an algorithm for retrospective causal learning and found that mesolimbic dopamine release conveys causal associations but not RPE, thereby challenging the dominant theory of reward learning. Our results reshape the conceptual and biological framework for associative learning.
Topics: Animals; Dopamine; Reward; Limbic System; Association Learning; Cues; Mice
PubMed: 36480599
DOI: 10.1126/science.abq6740 -
International Journal of Molecular... Jun 2019Chronic pain is a condition in which pain progresses from an acute to chronic state and persists beyond the healing process. Chronic pain impairs function and decreases... (Review)
Review
Chronic pain is a condition in which pain progresses from an acute to chronic state and persists beyond the healing process. Chronic pain impairs function and decreases patients' quality of life. In recent years, efforts have been made to deepen our understanding of chronic pain and to develop better treatments to alleviate chronic pain. In this review, we summarize the results of previous studies, focusing on the mechanisms underlying chronic pain development and the identification of neural areas related to chronic pain. We review the association between chronic pain and negative affective states. Further, we describe the structural and functional changes in brain structures that accompany the chronification of pain and discuss various neurotransmitter families involved. Our review aims to provide guidance for the development of future therapeutic approaches that could be used in the management of chronic pain.
Topics: Affect; Animals; Biomarkers; Brain; Cerebral Cortex; Chronic Pain; Disease Management; Humans; Limbic System; Neural Pathways; Signal Transduction
PubMed: 31248061
DOI: 10.3390/ijms20133130 -
Neuron Apr 2022The empathic ability to vicariously experience the other's fearful situation, a process called observational fear (OF), is critical to survive in nature and function in...
The empathic ability to vicariously experience the other's fearful situation, a process called observational fear (OF), is critical to survive in nature and function in society. OF can be facilitated by both prior similar fear experience in the observer and social familiarity with the demonstrator. However, the neural circuit mechanisms of experience-dependent OF (Exp OF) remain unknown. Here, we demonstrate that hippocampal-basolateral amygdala (HPC-BLA) circuits in mice without involving the anterior cingulate cortex, considered a center of OF, mediate Exp OF. Dorsal HPC neurons generate fear memory engram cells in BLA encoding prior similar fear experiences, which are essential for Exp OF. On the other hand, ventral HPC neurons respond to the familiar demonstrator's aversive situation during Exp OF, which reactivates the fear memory engram cells in BLA to elicit Exp OF. Our study provides new insights into the memory engram-dependent perception-action coupling that underlies empathic behaviors like Exp OF.
Topics: Amygdala; Animals; Basolateral Nuclear Complex; Fear; Gyrus Cinguli; Hippocampus; Mice
PubMed: 35139362
DOI: 10.1016/j.neuron.2022.01.019