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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 -
Physiological Reviews Apr 2016Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear... (Review)
Review
Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.
Topics: Amygdala; Animals; Conditioning, Psychological; Extinction, Psychological; Fear; Hippocampus; Hormones; Humans; Limbic System; Memory Consolidation; Neuronal Plasticity; Neurotransmitter Agents; Prefrontal Cortex; Stress Disorders, Post-Traumatic; Synapses
PubMed: 26983799
DOI: 10.1152/physrev.00018.2015 -
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 -
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 -
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 -
Neuroscience Letters May 2019Pain has a strong emotional component and is defined by its unpleasantness. Chronic pain represents a complex disorder with anxio-depressive symptoms and cognitive... (Review)
Review
Pain has a strong emotional component and is defined by its unpleasantness. Chronic pain represents a complex disorder with anxio-depressive symptoms and cognitive deficits. Underlying mechanisms are still not well understood but an important role for interactions between prefrontal cortical areas and subcortical limbic structures has emerged. Evidence from preclinical studies in the rodent brain suggests that neuroplastic changes in prefrontal (anterior cingulate, prelimbic and infralimbic) cortical and subcortical (amygdala and nucleus accumbens) brain areas and their interactions (corticolimbic circuitry) contribute to the complexity and persistence of pain and may be predetermining factors as has been proposed in recent human neuroimaging studies.
Topics: Animals; Humans; Limbic System; Pain; Prefrontal Cortex
PubMed: 30503916
DOI: 10.1016/j.neulet.2018.11.037 -
Neuron Jan 2019Ventral tegmental area (VTA) dopamine (DA) neurons play a central role in mediating motivated behaviors, but the circuitry through which they signal positive and...
Ventral tegmental area (VTA) dopamine (DA) neurons play a central role in mediating motivated behaviors, but the circuitry through which they signal positive and negative motivational stimuli is incompletely understood. Using in vivo fiber photometry, we simultaneously recorded activity in DA terminals in different nucleus accumbens (NAc) subnuclei during an aversive and reward conditioning task. We find that DA terminals in the ventral NAc medial shell (vNAcMed) are excited by unexpected aversive outcomes and to cues that predict them, whereas DA terminals in other NAc subregions are persistently depressed. Excitation to reward-predictive cues dominated in the NAc lateral shell and was largely absent in the vNAcMed. Moreover, we demonstrate that glutamatergic (VGLUT2-expressing) neurons in the lateral hypothalamus represent a key afferent input for providing information about aversive outcomes to vNAcMed-projecting DA neurons. Collectively, we reveal the distinct functional contributions of separate mesolimbic DA subsystems and their afferent pathways underlying motivated behaviors. VIDEO ABSTRACT.
Topics: Animals; Avoidance Learning; Dopaminergic Neurons; Limbic System; Male; Mesencephalon; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Organ Culture Techniques; Photometry; Ventral Tegmental Area; Vesicular Glutamate Transport Protein 2
PubMed: 30503173
DOI: 10.1016/j.neuron.2018.11.005 -
Neurobiology of Learning and Memory Mar 2022Increasing evidence has shown that noise overexposure could lead to impaired hippocampal function. Hippocampal alteration is also observed in several auditory deficits,... (Review)
Review
Increasing evidence has shown that noise overexposure could lead to impaired hippocampal function. Hippocampal alteration is also observed in several auditory deficits, including hearing loss, and tinnitus. Therefore, the functions of hearing and cognition interact with each other. Here, we summarize the evidence that noise affects the hippocampus from aspects of behavior, neurogenesis, ultrastructure, neurotransmission, other biomarkers, and electrophysiology. We also address hippocampal alterations in auditory disorders, including hearing loss and tinnitus. Based on the current state of the field, we point out several aspects that need further investigation. This review is not only to provide a comprehensive summary of the current state of the field but to emphasize that hearing matters in cognition and pave the way for future research.
Topics: Auditory Pathways; Hippocampus; Humans; Neurogenesis; Noise; Tinnitus
PubMed: 35124220
DOI: 10.1016/j.nlm.2022.107589 -
Cells Jun 2021Pain is an unpleasant sensation that alerts one to the presence of obnoxious stimuli or sensations. These stimuli are transferred by sensory neurons to the dorsal root... (Review)
Review
Pain is an unpleasant sensation that alerts one to the presence of obnoxious stimuli or sensations. These stimuli are transferred by sensory neurons to the dorsal root ganglia-spinal cord and finally to the brain. Glial cells in the peripheral nervous system, astrocytes in the brain, dorsal root ganglia, and immune cells all contribute to the development, maintenance, and resolution of pain. Both innate and adaptive immune responses modulate pain perception and behavior. Neutrophils, microglial, and T cell activation, essential components of the innate and adaptive immune responses, can play both excitatory and inhibitory roles and are involved in the transition from acute to chronic pain. Immune responses may also exacerbate pain perception by modulating the function of the cortical-limbic brain regions involved in behavioral and emotional responses. The link between an emotional state and pain perception is larger than what is widely acknowledged. In positive psychological states, perception of pain along with other somatic symptoms decreases, whereas in negative psychological states, these symptoms may worsen. Sex differences in mechanisms of pain perception are not well studied. In this review, we highlight what is known, controversies, and the gaps in this field.
Topics: Animals; Astrocytes; Cerebral Cortex; Humans; Limbic System; Lymphocyte Activation; Microglia; Neurons; Neutrophil Activation; Neutrophils; Pain; T-Lymphocytes
PubMed: 34205372
DOI: 10.3390/cells10061553