Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.616
Filtrar
1.
Sci Data ; 8(1): 9, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446665

RESUMO

We present an electrophysiological dataset collected from the amygdalae of nine participants attending a visual dynamic stimulation of emotional aversive content. The participants were patients affected by epilepsy who underwent preoperative invasive monitoring in the mesial temporal lobe. Participants were presented with dynamic visual sequences of fearful faces (aversive condition), interleaved with sequences of neutral landscapes (neutral condition). The dataset contains the simultaneous recording of intracranial EEG (iEEG) and neuronal spike times and waveforms, and localization information for iEEG electrodes. Participant characteristics and trial information are provided. We technically validated this dataset and provide here the spike sorting quality metrics and the spectra of iEEG signals. This dataset allows the investigation of amygdalar response to dynamic aversive stimuli at multiple spatial scales, from the macroscopic EEG to the neuronal firing in the human brain.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Emoções , Epilepsia/fisiopatologia , Adulto , Tonsila do Cerebelo/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
PLoS One ; 15(10): e0237204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33075046

RESUMO

The amygdala, a subcortical structure known for social and emotional processing, consists of multiple subnuclei with unique functions and connectivity patterns. Tracer studies in adult macaques have shown that the basolateral subnuclei differentially connect to parts of visual cortex, with stronger connections to anterior regions and weaker connections to posterior regions; infant macaques show robust connectivity even with posterior visual regions. Do these developmental differences also exist in the human amygdala, and are there specific functional regions that undergo the most pronounced developmental changes in their connections with the amygdala? To address these questions, we explored the functional connectivity (from resting-state fMRI data) of the basolateral amygdala to occipitotemporal cortex in human neonates scanned within one week of life and compared the connectivity patterns to those observed in young adults. Specifically, we calculated amygdala connectivity to anterior-posterior gradients of the anatomically-defined occipitotemporal cortex, and also to putative occipitotemporal functional parcels, including primary and high-level visual and auditory cortices (V1, A1, face, scene, object, body, high-level auditory regions). Results showed a decreasing gradient of functional connectivity to the occipitotemporal cortex in adults-similar to the gradient seen in macaque tracer studies-but no such gradient was observed in neonates. Further, adults had stronger connections to high-level functional regions associated with face, body, and object processing, and weaker connections to primary sensory regions (i.e., A1, V1), whereas neonates showed the same amount of connectivity to primary and high-level sensory regions. Overall, these results show that functional connectivity between the amygdala and occipitotemporal cortex is not yet differentiated in neonates, suggesting a role of maturation and experience in shaping these connections later in life.


Assuntos
Tonsila do Cerebelo/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologia , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Conectoma , Vias Neurais/fisiologia , Lobo Occipital/fisiologia , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
3.
Nat Commun ; 11(1): 5207, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060630

RESUMO

Fear conditioning is a form of associative learning that is known to involve different brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memories, indicating an important role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. Moreover, FN-vlPAG projections also modulate extinction learning. We also found a FN-parafascicular thalamus pathway, which may relay cerebellar influence to the amygdala and modulates anxiety behaviors. Overall, our results reveal multiple contributions of the cerebellum to the emotional system.


Assuntos
Sistema Nervoso Central/fisiologia , Medo/fisiologia , Memória/fisiologia , Vias Neurais/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Sistema Nervoso Central/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiologia , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Aprendizagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética
4.
Nat Commun ; 11(1): 4358, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868768

RESUMO

Learned fear and safety are associated with distinct oscillatory states in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). To determine if and how these network states support the retrieval of competing memories, we mimicked endogenous oscillatory activity through optogenetic stimulation of parvalbumin-expressing interneurons in mice during retrieval of contextual fear and extinction memories. We found that exogenously induced 4 Hz and 8 Hz oscillatory activity in the BLA exerts bi-directional control over conditioned freezing behavior in an experience- and context-specific manner, and that these oscillations have an experience-dependent ability to recruit distinct functional neuronal ensembles. At the network level we demonstrate, via simultaneous manipulation of BLA and mPFC, that experience-dependent 4 Hz resonance across BLA-mPFC circuitry supports post-extinction fear memory retrieval. Our findings reveal that post-extinction fear memory retrieval is supported by local and interregional experience-dependent resonance, and suggest novel approaches for interrogation and therapeutic manipulation of acquired fear circuitry.


Assuntos
Tonsila do Cerebelo/fisiologia , Extinção Psicológica , Medo/fisiologia , Memória/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/fisiologia , Condicionamento Psicológico , Eletrofisiologia/métodos , Aprendizagem/fisiologia , Camundongos , Optogenética/métodos , Córtex Pré-Frontal/fisiologia
5.
Adv Exp Med Biol ; 1284: 43-48, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32852739

RESUMO

Social behavior is a complex behavior that requires processing of sensory cues and integration of internal states. Social interaction involves two or more individuals to approach each other and engage communications. Although sensory, motivational, emotional, or reward cues may all play roles in directing the sociability and social preference during social interaction, how neural activities from different brain regions are modulated during the behavioral process of social interaction are only beginning to be studied. Multiple brain regions including prefrontal cortex, hippocampus, and amygdala contain active neurons during social interaction. This review examines the neural responses in behaving rodents during social behavior and discusses how manipulation of specific neural pathways can modulate social behavior. Neural activities during social interaction provide direct measurements about how social information is coded and are beneficial in understanding the neural mechanisms underlying social behavior.


Assuntos
Neurônios/fisiologia , Comportamento Social , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/fisiologia , Animais , Modelos Animais , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Recompensa
6.
Proc Natl Acad Sci U S A ; 117(34): 20868-20873, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32764147

RESUMO

Adaptive social behavior and mental well-being depend on not only recognizing emotional expressions but also, inferring the absence of emotion. While the neurobiology underwriting the perception of emotions is well studied, the mechanisms for detecting a lack of emotional content in social signals remain largely unknown. Here, using cutting-edge analyses of effective brain connectivity, we uncover the brain networks differentiating neutral and emotional body language. The data indicate greater activation of the right amygdala and midline cerebellar vermis to nonemotional as opposed to emotional body language. Most important, the effective connectivity between the amygdala and insula predicts people's ability to recognize the absence of emotion. These conclusions extend substantially current concepts of emotion perception by suggesting engagement of limbic effective connectivity in recognizing the lack of emotion in body language reading. Furthermore, the outcome may advance the understanding of overly emotional interpretation of social signals in depression or schizophrenia by providing the missing link between body language reading and limbic pathways. The study thus opens an avenue for multidisciplinary research on social cognition and the underlying cerebrocerebellar networks, ranging from animal models to patients with neuropsychiatric conditions.


Assuntos
Emoções/fisiologia , Cinésica , Transtornos Mentais/fisiopatologia , Adulto , Tonsila do Cerebelo/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Expressão Facial , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Vias Neurais/fisiologia , Estimulação Luminosa/métodos
7.
Nat Neurosci ; 23(9): 1111-1124, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32719562

RESUMO

Sexual and aggressive behaviors are fundamental to animal survival and reproduction. The medial preoptic nucleus (MPN) and ventrolateral part of the ventromedial hypothalamus (VMHvl) are essential regions for male sexual and aggressive behaviors, respectively. While key inhibitory inputs to the VMHvl and MPN have been identified, the extrahypothalamic excitatory inputs essential for social behaviors remain elusive. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the posterior amygdala (PA) as a main source of excitatory inputs to the hypothalamus and key mediators for mating and fighting in male mice. We find two largely distinct PA subpopulations that differ in connectivity, gene expression, in vivo responses and social behavior relevance. MPN-projecting PAEsr1+ cells are activated during mating and are necessary and sufficient for male sexual behaviors, while VMHvl-projecting PAEsr1+ cells are excited during intermale aggression and promote attacks. These findings place the PA as a key node in both male aggression and reproduction circuits.


Assuntos
Agressão/fisiologia , Tonsila do Cerebelo/fisiologia , Vias Neurais/fisiologia , Comportamento Sexual Animal/fisiologia , Tonsila do Cerebelo/citologia , Animais , Hipotálamo/citologia , Hipotálamo/fisiologia , Masculino , Camundongos , Vias Neurais/citologia , Neurônios/citologia , Neurônios/fisiologia
8.
Neuron ; 107(4): 717-730.e5, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32562662

RESUMO

The prelimbic (PL) area and basolateral amygdala (lateral [LA] and basolateral [BL] nuclei) have closely related functions and similar extrinsic connectivity. Reasoning that the computational advantage of such redundancy should be reflected in differences in how these structures represent information, we compared the coding properties of PL and amygdala neurons during a task that requires rats to produce different conditioned defensive or appetitive behaviors. Rather than unambiguous regional differences in the identities of the variables encoded, we found gradients in how the same variables are represented. Whereas PL and BL neurons represented many different parameters through minor variations in firing rates, LA cells coded fewer task features with stronger changes in activity. At the population level, whereas valence could be easily distinguished from amygdala activity, PL neurons could distinguish both valence and trial identity as well as or better than amygdala neurons. Thus, PL has greater representational capacity.


Assuntos
Potenciais de Ação/fisiologia , Tonsila do Cerebelo/fisiologia , Aprendizagem da Esquiva/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Comportamento Animal/fisiologia , Medo/fisiologia , Modelos Neurológicos , Vias Neurais/fisiologia , Ratos , Recompensa
9.
Nat Commun ; 11(1): 2847, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504036

RESUMO

The browning of white adipose tissue (WAT) has got much attention for its potential beneficial effects on metabolic disorders, however, the nutritional factors and neuronal signals involved remain largely unknown. We sought to investigate whether WAT browning is stimulated by leucine deprivation, and whether the amino acid sensor, general control non-derepressible 2 (GCN2), in amygdalar protein kinase C-δ (PKC-δ) neurons contributes to this regulation. Our results show that leucine deficiency can induce WAT browning, which is unlikely to be caused by food intake, but is largely blocked by PKC-δ neuronal inhibition and amygdalar GCN2 deletion. Furthermore, GCN2 knockdown in amygdalar PKC-δ neurons blocks WAT browning, which is reversed by over-expression of amino acid responsive gene activating transcription factor 4 (ATF4), and is mediated by the activities of amygdalar PKC-δ neurons and the sympathetic nervous system. Our data demonstrate that GCN2/ATF4 can regulate WAT browning in amygdalar PKC-δ neurons under leucine deprivation.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Tecido Adiposo Branco/fisiologia , Tonsila do Cerebelo/fisiologia , Leucina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/inervação , Tonsila do Cerebelo/citologia , Animais , Técnicas de Silenciamento de Genes , Lipólise/fisiologia , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Proteína Quinase C-delta/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/fisiologia , Técnicas Estereotáxicas , Sistema Nervoso Simpático/fisiologia , Termogênese/fisiologia
10.
J Neurosci ; 40(26): 5051-5062, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32371606

RESUMO

Peripheral sources of individual variation in taste intensity perception have been well described. The existence of a central source has been proposed but remains unexplored. Here we used functional magnetic resonance imaging in healthy human participants (20 women, 8 men) to evaluate the hypothesis that the amygdala exerts an inhibitory influence that affects the "gain" of the gustatory system during tasting. Consistent with the existence of a central gain mechanism (CGM), we found that central amygdala response was correlated with mean intensity ratings across multiple tastants. In addition, psychophysiological and dynamic causal modeling analyses revealed that the connection strength between inhibitory outputs from amygdala to medial dorsal and ventral posterior medial thalamus predicted individual differences in responsiveness to taste stimulation. These results imply that inhibitory inputs from the amygdala to the thalamus act as a CGM that influences taste intensity perception.SIGNIFICANCE STATEMENT Whether central circuits contribute to individual variation in taste intensity perception is unknown. Here we used functional magnetic resonance imaging in healthy human participants to identify an amygdala-thalamic circuit where network dynamics and connectivity strengths during tasting predict individual variation in taste intensity ratings. This finding implies that individual differences in taste intensity perception do not arise solely from variation in peripheral gustatory factors.


Assuntos
Tonsila do Cerebelo/fisiologia , Vias Neurais/fisiologia , Percepção Gustatória/fisiologia , Tálamo/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
11.
J Neurosci ; 40(24): 4761-4772, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32376780

RESUMO

The amygdala plays an important role in many aspects of social cognition and reward learning. Here, we aimed to determine whether human amygdala neurons are involved in the computations necessary to implement learning through observation. We performed single-neuron recordings from the amygdalae of human neurosurgical patients (male and female) while they learned about the value of stimuli through observing the outcomes experienced by another agent interacting with those stimuli. We used a detailed computational modeling approach to describe patients' behavior in the task. We found a significant proportion of amygdala neurons whose activity correlated with both expected rewards for oneself and others, and in tracking outcome values received by oneself or other agents. Additionally, a population decoding analysis suggests the presence of information for both observed and experiential outcomes in the amygdala. Encoding and decoding analyses suggested observational value coding in amygdala neurons occurred in a different subset of neurons than experiential value coding. Collectively, these findings support a key role for the human amygdala in the computations underlying the capacity for learning through observation.SIGNIFICANCE STATEMENT Single-neuron studies of the human brain provide a unique window into the computational mechanisms of cognition. In this study, epilepsy patients implanted intracranially with hybrid depth electrodes performed an observational learning (OL) task. We measured single-neuron activity in the amygdala and found a representation for observational rewards as well as observational expected reward values. Additionally, distinct subsets of amygdala neurons represented self-experienced and observational values. This study provides a rare glimpse into the role of human amygdala neurons in social cognition.


Assuntos
Tonsila do Cerebelo/fisiologia , Aprendizagem/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Cognição/fisiologia , Feminino , Humanos , Masculino , Percepção Social
12.
Nat Commun ; 11(1): 2221, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376858

RESUMO

Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.


Assuntos
Tonsila do Cerebelo/fisiologia , Ansiedade/fisiopatologia , Ácido Glutâmico/metabolismo , Vias Neurais/fisiologia , Córtex Pré-Frontal/fisiologia , Estresse Psicológico , Animais , Ansiedade/metabolismo , Complexo Nuclear Basolateral da Amígdala/fisiologia , Corticosterona/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética , Restrição Física
13.
J Neurosci ; 40(27): 5264-5272, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32457069

RESUMO

One of the strongest drivers of food consumption is pleasure, and with a large variety of palatable food continuously available, there is rarely any necessity to eat something not tasty. The amygdala is involved in hedonic valuation, but its role in valence assignment during food choices is less understood. Given recent evidence for spatially segregated amygdala signatures encoding palatability, we applied a multivariate approach on fMRI data to extract valence-specific signal patterns during an explicit evaluation of food liking. These valence localizers were then used to identify hedonic valuation processes while the same healthy human participants (14 female, 16 male; in overnight fasted state on both scanning days) performed a willingness-to-eat task in a separate fMRI measurement. Valence-specific patterns of amygdala signaling predicted decisions on food consumption significantly. Findings could be validated using the same valence localizers to predict consumption decisions participants made on a separate set of food stimuli that had not been used for localizer identification. Control analyses revealed these findings to be restricted to a multivariate compared with a univariate approach, and to be specific for valence processing in the amygdala. Spatially distributed valuation signals of the amygdala thus appear to modulate appetitive consumption decisions, and may be useful to identify current hedonic valuation processes triggering food choices even when not explicitly instructed.SIGNIFICANCE STATEMENT The expectation of tastiness is a particularly strong driver in everyday decisions on food consumption. The amygdala is important for hedonic valuation processes and involved in valence-related behavior, but the relationship between both processes is less understood. Here, we show that hedonic values of food are represented in spatially distributed activation patterns in the amygdala. The engagement of these patterns during food choices modulates consumption decisions. Findings are stable in a separate stimulus set. These results suggest that valence-specific amygdala signals are integrated into the formation of food choices.


Assuntos
Tonsila do Cerebelo/fisiologia , Ingestão de Alimentos/fisiologia , Ingestão de Alimentos/psicologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tomada de Decisões/fisiologia , Impulso (Psicologia) , Jejum/psicologia , Feminino , Alimentos , Preferências Alimentares , Humanos , Imagem por Ressonância Magnética , Masculino , Prazer , Adulto Jovem
14.
Proc Natl Acad Sci U S A ; 117(21): 11781-11787, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32385158

RESUMO

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.


Assuntos
Tonsila do Cerebelo , Medo/efeitos dos fármacos , Lorazepam/farmacologia , Ocitocina/farmacologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Medo/fisiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Neurotransmissores/farmacologia , Adulto Jovem
15.
J Neurosci ; 40(18): 3646-3656, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32238480

RESUMO

As an important cognitive bias, the framing effect shows that our decision preferences are sensitive to the verbal description (i.e., frame) of options. This study focuses on the neural underpinnings of the social framing effect, which is based on decision-making regarding other people. A novel paradigm was used in which participants made a trade-off between economic benefits and the feelings of others. This decision was described as either a "harm" to, or "not helping," other persons in two conditions (Harm frame vs Help frame). Both human males and females were recruited. Participants behaved more prosocially for Harm frame compared with Help frame, resulting in a significant social framing effect. Using functional magnetic resonance imaging, Experiment 1 showed that the social framing effect was associated with stronger activation in the temporoparietal junction (TPJ), especially its right part. The functional connectivity between the right TPJ (rTPJ) and medial prefrontal cortex predicted the social framing effect on the group level. In Experiment 2, we used transcranial direct current stimulation to modulate the activity of the rTPJ and found that the social framing effect became more prominent under anodal (excitatory) stimulation, while the nonsocial framing effect elicited by the economic gain/loss gambling frame remained unaffected. The rTPJ results might be associated with moral conflicts modulated by the social consequences of an action or different levels of mentalizing with others under different frame conditions, but alternative interpretations are also worth noting. These findings could help elucidate the psychological mechanisms of the social framing effect.SIGNIFICANCE STATEMENT Previous studies have suggested that the framing effect is generated from an interaction between the amygdala and anterior cingulate cortex. This opinion, however, is based on findings from nonsocial framing tasks. Recent research has highlighted the importance of distinguishing between the social and nonsocial framing effects. The current study focuses on the social framing effect and finds out that the temporoparietal junction and its functional connectivity with the medial prefrontal cortex play a significant role. Additionally, modulating the activity of this region leads to changes in social (but not nonsocial) framing effect. Broadly speaking, these findings help understand the difference in neural mechanisms between social and nonsocial decision-making. Meanwhile, they might be illuminating to promote helping behavior in society.


Assuntos
Tonsila do Cerebelo/fisiologia , Tomada de Decisões/fisiologia , Imagem por Ressonância Magnética/métodos , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Tonsila do Cerebelo/diagnóstico por imagem , Feminino , Humanos , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
16.
J Neurosci ; 40(20): 3969-3980, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32277045

RESUMO

The amygdala is a brain area critical for the formation of fear memories. However, the nature of the teaching signal(s) that drive plasticity in the amygdala are still under debate. Here, we use optogenetic methods to investigate the contribution of ventral tegmental area (VTA) dopamine neurons to auditory-cued fear learning in male mice. Using anterograde and retrograde labeling, we found that a sparse and relatively evenly distributed population of VTA neurons projects to the basal amygdala (BA). In vivo optrode recordings in behaving mice showed that many VTA neurons, among them putative dopamine neurons, are excited by footshocks, and acquire a response to auditory stimuli during fear learning. Combined cfos imaging and retrograde labeling in dopamine transporter (DAT) Cre mice revealed that a large majority of BA projectors (>95%) are dopamine neurons, and that BA projectors become activated by the tone-footshock pairing of fear learning protocols. Finally, silencing VTA dopamine neurons, or their axon terminals in the BA during the footshock, reduced the strength of fear memory as tested 1 d later, whereas silencing the VTA-central amygdala (CeA) projection had no effect. Thus, VTA dopamine neurons projecting to the BA contribute to fear memory formation, by coding for the saliency of the footshock event and by signaling such events to the basal amygdala.SIGNIFICANCE STATEMENT Powerful mechanisms of fear learning have evolved in animals and humans to enable survival. During fear conditioning, a sensory cue, such as a tone (the conditioned stimulus), comes to predict an innately aversive stimulus, such as a mild footshock (the unconditioned stimulus). A brain representation of the unconditioned stimulus must act as a teaching signal to instruct plasticity of the conditioned stimulus representation in fear-related brain areas. Here we show that dopamine neurons in the VTA that project to the basal amygdala contribute to such a teaching signal for plasticity, thereby facilitating the formation of fear memories. Knowledge about the role of dopamine in aversively motivated plasticity might allow further insights into maladaptive plasticities that underlie anxiety and post-traumatic stress disorders in humans.


Assuntos
Tonsila do Cerebelo/fisiologia , Neurônios Dopaminérgicos/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Medo/fisiologia , Medo/psicologia , Aprendizagem/fisiologia , Área Tegmentar Ventral/fisiologia , Estimulação Acústica , Animais , Sinais (Psicologia) , Proteínas da Membrana Plasmática de Transporte de Dopamina , Fenômenos Eletrofisiológicos/fisiologia , Eletrochoque , Masculino , Camundongos , Neuroimagem
17.
Sci Rep ; 10(1): 5871, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245993

RESUMO

The amygdala facilitates odor driven behavioral responses by enhancing the saliency of olfactory signals. Before this processing, olfactory input is refined through the feedback provided by amygdala corticofugal projection (ACPs). Although the saliency of odor signals is subject to developmental changes, the stage at which this cortical feedback first occurs is not known. Using optogenetically-assisted intracellular recordings of the mouse cortical amygdala, we identified changes in the electrophysiological properties of ACPs at different developmental stages. These were consistent with a decrease in neuronal excitability and an increase in the amount of incoming accessory olfactory bulb (AOB) inputs, as confirmed by estimates of release probability, quantal size and contact number at the AOB-to-ACP synapse. Moreover, the proportion of ACPs activated in response to odors was dependent on the stage of development as revealed by c-Fos expression analysis. These results update standard accounts of how the amygdala processes social signals by emphasizing the occurrence of critical periods in the development of its sensory gating functions.


Assuntos
Tonsila do Cerebelo/fisiologia , Vias Neurais/fisiologia , Olfato/fisiologia , Animais , Fenômenos Eletrofisiológicos , Retroalimentação Fisiológica/fisiologia , Feminino , Masculino , Camundongos , Odorantes , Bulbo Olfatório/fisiologia , Optogenética , Sinapses/fisiologia
18.
J Neurosci ; 40(20): 3981-3994, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32284340

RESUMO

Male animals may show alternative behaviors toward infants: attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state, including the hormonal environment and/or social experiences. Converging data suggest that the medial preoptic area (MPOA) contributes to the behavioral selection toward the pup. However, the neural mechanisms underlying how integrated stimuli affect the MPOA-dependent behavioral selection remain unclear. Here we focus on the amygdalohippocampal area (AHi) that projects to MPOA and expresses oxytocin receptor, a hormone receptor mediating social behavior toward pups. We describe the activation of MPOA-projection AHi neurons in male mice by social contact with pups. Input mapping using the TRIO method reveals that MPOA-projection AHi neurons receive prominent inputs from several regions, including the thalamus, hypothalamus, and olfactory cortex. Electrophysiological and histologic analysis demonstrates that oxytocin modulates inhibitory synaptic responses on MPOA-projection AHi neurons. In addition, AHi forms the excitatory monosynapse to MPOA, and pharmacological activation of MPOA-projection AHi neurons enhances only aggressive behavior, but not parental behavior. Interestingly, this promoted behavior was related to social experience in male mice. Collectively, our results identified a presynaptic partner of MPOA that can integrate sensory input and hormonal state, and trigger pup-directed aggression.SIGNIFICANCE STATEMENT The medial preoptic area (MPOA) plays critical roles in parental behavior, such as motor control, motivation, and social interaction. The MPOA projects to multiple brain regions, and these projections contribute to several neural controls in parental behavior. In contrast, how inputs to MPOA are regulated by social and environmental information is poorly understood. In this study, we focus on the amygdalohippocampal area (AHi) that connects to MPOA and expresses oxytocin receptor. We demonstrate the disruption of the expression of parental behavior triggered by the activation of MPOA-projection AHi neurons. This behavior may be regulated not only by oxytocin but also by neural input from several regions.


Assuntos
Agressão/fisiologia , Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Área Pré-Óptica/fisiologia , Tonsila do Cerebelo/citologia , Animais , Mapeamento Encefálico , Fenômenos Eletrofisiológicos , Hipocampo/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibição Neural , Comportamento Paterno , Área Pré-Óptica/citologia , Receptores de Ocitocina/metabolismo , Comportamento Social , Meio Social
19.
Behav Neurosci ; 134(2): 153-165, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32175761

RESUMO

The amygdala plays an essential role in evaluating social information, threat detection, and learning fear associations. Yet, most of that knowledge comes from studies in adult humans and animals with a fully developed amygdala. Given the considerable protracted postnatal development of the amygdala, it is important to understand how early damage to this structure may impact the long-term development of behavior. The current study examined behavioral responses toward social, innate, or learned aversive stimuli among neonatal amygdala lesion (Neo-Aibo; males = 3, females = 3) or sham-operated control (Neo-C; males = 3, females = 4) rhesus macaques. Compared with controls, Neo-Aibo animals exhibited less emotional reactivity toward aversive objects, including faster retrieval of food reward, fewer fearful responses, and more manipulation of objects. This lower reactivity was only seen in response to social and innate aversive stimuli, whereas Neo-Aibo animals had similar responses to controls for learned aversive stimuli. The current study also detected sex differences in behavioral response to aversive stimuli, such that, as compared with males, females took longer to retrieve the food reward across all aversive stimuli types, but only expressed more hostility and more coo vocalizations during learned aversive trials. Early amygdala damage impacted the expression of some, but not all, sex differences. For example, neonatal amygdala damage eliminated the sex difference in object manipulation. These findings add important information that broaden our understanding of the role of the amygdala in the expression of sexually dimorphic behaviors, as well as its role in learning fear associations and threat detection. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Assuntos
Tonsila do Cerebelo/fisiologia , Emoções/fisiologia , Medo/fisiologia , Caracteres Sexuais , Comportamento Social , Tonsila do Cerebelo/patologia , Animais , Animais Recém-Nascidos , Aprendizagem da Esquiva , Comportamento Animal/fisiologia , Feminino , Macaca mulatta , Masculino
20.
Nat Commun ; 11(1): 1382, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170133

RESUMO

In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal-amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1-BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1-BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.


Assuntos
Tonsila do Cerebelo/fisiologia , Medo/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Vias Neurais/fisiologia , Amnésia/induzido quimicamente , Amnésia/metabolismo , Amnésia/patologia , Animais , Aprendizagem da Esquiva/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologia , Comportamento Animal/fisiologia , Região CA1 Hipocampal/fisiologia , Modelos Animais de Doenças , Aprendizagem/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Vias Neurais/citologia , Plasticidade Neuronal , Neurônios/citologia , Neurônios/fisiologia , Sinapses/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA