RESUMEN
Memories about sensory experiences are tightly linked to the context in which they were formed. Memory contextualization is fundamental for the selection of appropriate behavioral reactions needed for survival, yet the underlying neuronal circuits are poorly understood. By combining trans-synaptic viral tracing and optogenetic manipulation, we found that the ventral hippocampus (vHC) and the amygdala, two key brain structures encoding context and emotional experiences, interact via multiple parallel pathways. A projection from the vHC to the basal amygdala mediates fear behavior elicited by a conditioned context, whereas a parallel projection from a distinct subset of vHC neurons onto midbrain-projecting neurons in the central amygdala is necessary for context-dependent retrieval of cued fear memories. Our findings demonstrate that two fundamentally distinct roles of context in fear memory retrieval are processed by distinct vHC output pathways, thereby allowing for the formation of robust contextual fear memories while preserving context-dependent behavioral flexibility.
Asunto(s)
Amígdala del Cerebelo/fisiología , Hipocampo/fisiología , Memoria , Vías Nerviosas , Animales , Condicionamiento Psicológico , Fenómenos Electrofisiológicos , Miedo , Ratones , Ratones Endogámicos C57BL , Neuronas/citología , Neuronas/fisiología , Optogenética , Virus de la Rabia/genética , SinapsisRESUMEN
Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder1. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA)2; however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat. Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight. Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.
Asunto(s)
Reacción de Prevención , Núcleo Amigdalino Central , Vías Nerviosas , Neuronas , Reacción de Prevención/fisiología , Núcleo Amigdalino Central/citología , Núcleo Amigdalino Central/fisiología , Neuronas/fisiología , Corteza Prefrontal/citología , Corteza Prefrontal/fisiología , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Ácido Glutámico/metabolismo , Vías Nerviosas/fisiología , Calcio/análisis , Electrofisiología , Puente/citología , Puente/fisiologíaRESUMEN
When faced with threat, the survival of an organism is contingent upon the selection of appropriate active or passive behavioural responses. Freezing is an evolutionarily conserved passive fear response that has been used extensively to study the neuronal mechanisms of fear and fear conditioning in rodents. However, rodents also exhibit active responses such as flight under natural conditions. The central amygdala (CEA) is a forebrain structure vital for the acquisition and expression of conditioned fear responses, and the role of specific neuronal sub-populations of the CEA in freezing behaviour is well-established. Whether the CEA is also involved in flight behaviour, and how neuronal circuits for active and passive fear behaviour interact within the CEA, are not yet understood. Here, using in vivo optogenetics and extracellular recordings of identified cell types in a behavioural model in which mice switch between conditioned freezing and flight, we show that active and passive fear responses are mediated by distinct and mutually inhibitory CEA neurons. Cells expressing corticotropin-releasing factor (CRF+) mediate conditioned flight, and activation of somatostatin-positive (SOM+) neurons initiates passive freezing behaviour. Moreover, we find that the balance between conditioned flight and freezing behaviour is regulated by means of local inhibitory connections between CRF+ and SOM+ neurons, indicating that the selection of appropriate behavioural responses to threat is based on competitive interactions between two defined populations of inhibitory neurons, a circuit motif allowing for rapid and flexible action selection.
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Reacción de Fuga/fisiología , Miedo/fisiología , Miedo/psicología , Reacción Cataléptica de Congelación/fisiología , Inhibición Neural , Neuronas/fisiología , Animales , Núcleo Amigdalino Central/citología , Núcleo Amigdalino Central/fisiología , Hormona Liberadora de Corticotropina/metabolismo , Locomoción/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Neurológicos , Vías Nerviosas , Optogenética , Somatostatina/metabolismoRESUMEN
Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.
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Reacción de Fuga/fisiología , Reacción Cataléptica de Congelación/fisiología , Vías Nerviosas/citología , Vías Nerviosas/fisiología , Sustancia Gris Periacueductal/citología , Sustancia Gris Periacueductal/fisiología , Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Animales , Neuronas GABAérgicas/fisiología , Ácido Glutámico/metabolismo , Masculino , Bulbo Raquídeo/citología , Bulbo Raquídeo/fisiología , Ratones , Ratones Endogámicos C57BL , Inhibición Neural/fisiología , Técnicas de Trazados de Vías Neuroanatómicas , OptogenéticaRESUMEN
Social species form dominance hierarchies to ensure survival and promote reproductive success. Traditionally studied in males, rodent hierarchies are considered despotic, and dominant social rank results from a history of winning agonistic encounters. By contrast, female hierarchies are thought to be less despotic, and rank is conferred by intrinsic traits. Both social buffering and elevated social status confer resilience to depression, anxiety, and other consequences of chronic stress. Here, we investigate whether female social hierarchies and individual traits related to social rank likewise influence stress resilience. We observe the formation of dyadic female hierarchies under varying conditions of ambient light and circadian phase and subject mice to two forms of chronic psychosocial stress: social isolation or social instability. We find that stable female hierarchies emerge rapidly in dyads. Individual behavioral and endocrinological traits are characteristic of rank, some of which are circadian phase dependent. Further, female social rank is predicted by behavior and stress status prior to social introduction. Other behavioral characteristics suggest that rank is motivation-based, indicating that female rank identity serves an evolutionarily relevant purpose. Rank is associated with alterations in behavior in response to social instability stress and prolonged social isolation, but the different forms of stress produce disparate rank responses in endocrine status. Histological examination of c-Fos protein expression identified brain regions that respond to social novelty or social reunion following chronic isolation in a rank-specific manner. Collectively, female rank is linked to neurobiology, and hierarchies exert context-specific influence upon stress outcomes.
Asunto(s)
Predominio Social , Aislamiento Social , Masculino , Animales , Femenino , Ratones , Fenotipo , Ansiedad , Jerarquia SocialRESUMEN
Social behavior is complex and fundamental, and its deficits are common pathological features for several psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Acute stress may have a negative impact on social behavior, and these effects can vary based on sex. The aim of this study was to explore the effect of acute footshock stress, using analogous parameters to those commonly used in fear conditioning assays, on the sociability of male and female C57BL/6J mice in a standard social approach test. Animals were divided into two main groups of footshock stress (22 male, 24 female) and context exposed control (23 male and 22 female). Each group had mice that were treated intraperitoneally with either the benzodiazepine-alprazolam (control: 10 male, 10 female; stress: 11 male, 11 female), or vehicle (control: 13 male, 12 female; stress: 11 male, 13 female). In all groups, neuronal activation during social approach was assessed using immunohistochemistry against the immediate early gene product cFos. Although footshock stress did not significantly alter sociability or latency to approach a social stimulus, it did increase defensive tail-rattling behavior specifically in males (p = 0.0022). This stress-induced increase in tail-rattling was alleviated by alprazolam (p = 0.03), yet alprazolam had no effect on female tail-rattling behavior in the stress group. Alprazolam lowered cFos expression in the medial prefrontal cortex (p = 0.001 infralimbic area, p = 0.02 prelimbic area), and social approach induced sex-dependent differences in cFos activation in the ventromedial intercalated cell clusters (p = 0.04). Social approach following stress-induced cFos expression was positively correlated with latency to approach and negatively correlated with sociability in the prelimbic area and multiple amygdala subregions (all p < 0.05). Collectively, our results suggest that acute footshock stress induces sex-dependent alterations in defensiveness and differential patterns of cFos activation during social approach.
Asunto(s)
Alprazolam , Corteza Prefrontal , Masculino , Femenino , Ratones , Animales , Corteza Prefrontal/fisiología , Alprazolam/farmacología , Ratones Endogámicos C57BL , Amígdala del Cerebelo/fisiología , Conducta SocialRESUMEN
To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Heinz et al., 2017; Jikomes et al., 2016), these tasks required different behavioral responses to each stimulus. As many brain regions involved in survival behavior process stimuli of opposite valence, we developed a paradigm in which mice perform the same response (nosepoke) to distinct auditory cues to obtain a rewarding outcome (palatable food) or avoid an aversive outcome (mild footshoock). This design allows for both within- and between-subject comparisons as animals respond to appetitive and aversive cues. The central nucleus of the amygdala (CeA) is implicated in the regulation of responses to stimuli of either valence. Considering its role in threat processing (Haubensak et al., 2010; Wilensky et al., 2006) and regulation of incentive salience (Warlow and Berridge, 2021), it is important to examine the contribution of the CeA to mechanisms potentially underlying comorbid dysregulation of avoidance and reward (Bolton et al., 2009; Sinha, 2008). Using this paradigm, we tested the role of two molecularly defined CeA subtypes previously linked to consummatory and defensive behaviors. Significant strain differences in the acquisition and performance of the task were observed. Bidirectional chemogenetic manipulation of CeA somatostatin (SOM) neurons altered motivation for reward and perseveration of reward-seeking responses on avoidance trials. Manipulation of corticotropin-releasing factor neurons (CRF) had no significant effect on food reward consumption, motivation, or task performance. This paradigm will facilitate investigations into the neuronal mechanisms controlling motivated behavior across valences. Significance Statement: It is unclear how different neuronal populations contribute to reward- and aversion-driven behaviors within a subject. To address this question, we developed a novel behavioral paradigm in which mice obtain food and avoid footshocks via the same operant response. We then use this paradigm to test how the central amygdala coordinates appetitive and aversive behavioral responses. By testing somatostatin-IRES-Cre and CRF-IRES-Cre transgenic lines, we found significant differences between strains on task acquisition and performance. Using chemogenetics, we demonstrate that CeA SOM+ neurons regulate motivation for reward, while manipulation of CeA CRF+ neurons had no effect on task performance. Future studies investigating the interaction between positive and negative motivation circuits should benefit from the use of this dual valence paradigm.
RESUMEN
To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Jikomes et al., 2016; Heinz et al., 2017), these tasks required different behavioral responses to each stimulus. As many brain regions involved in survival behavior process stimuli of opposite valence, we developed a paradigm in which mice perform the same response (nose poke) to distinct auditory cues to obtain a rewarding outcome (palatable food) or avoid an aversive outcome (mild footshoock). This design allows for both within-subject and between-subject comparisons as animals respond to appetitive and aversive cues. The central nucleus of the amygdala (CeA) is implicated in the regulation of responses to stimuli of either valence. Considering its role in threat processing (Wilensky et al., 2006; Haubensak et al., 2010) and regulation of incentive salience (Warlow and Berridge, 2021), it is important to examine the contribution of the CeA to mechanisms potentially underlying comorbid dysregulation of avoidance and reward (Sinha, 2008; Bolton et al., 2009). Using this paradigm, we tested the role of two molecularly defined CeA subtypes previously linked to consummatory and defensive behaviors. Significant strain differences in the acquisition and performance of the task were observed. Bidirectional chemogenetic manipulation of CeA somatostatin (SOM) neurons altered motivation for reward and perseveration of reward-seeking responses on avoidance trials. Manipulation of corticotropin-releasing factor neurons (CRF) had no significant effect on food reward consumption, motivation, or task performance. This paradigm will facilitate investigations into the neuronal mechanisms controlling motivated behavior across valences.
Asunto(s)
Núcleo Amigdalino Central , Animales , Ratones , Condicionamiento Operante , Motivación , Afecto , NeuronasRESUMEN
Dopamine-producing neurons fire with both basal level tonic patterns and phasic bursts. Varying affinities of the five dopamine receptors have led to a hypothesis that higher affinity receptors are primarily activated by basal level tonic dopamine, while lower affinity receptors may be tuned to be sensitive to higher levels caused by phasic bursts. Genetically modified mice provide a method to begin to probe this hypothesis. Here we discuss three mouse models. Dopamine-deficient mice were used to determine which behaviors require dopamine. These behaviors were then analyzed in mice lacking D1 receptors and in mice with reduced phasic dopamine release. Comparison of the latter two mouse models revealed a similar failure to learn about and respond normally to cues that indicate either a positive or negative outcome, giving support to the hypothesis that phasic dopamine release and the D1 receptor act in the same pathway. However, the D1 receptor likely has additional roles beyond those of phasic dopamine detection, because D1 receptor knockout mice have deficits in addition to what has been observed in mice with reduced phasic dopamine release.
Asunto(s)
Dopamina/metabolismo , Genética Conductual , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo , Transducción de Señal/fisiología , Animales , Condicionamiento Clásico , Aprendizaje/fisiología , Memoria/fisiología , Ratones , Ratones Noqueados , Actividad Motora/genética , Neuronas/metabolismoRESUMEN
Midbrain dopamine (DA) neurons fire in 2 characteristic modes, tonic and phasic, which are thought to modulate distinct aspects of behavior. However, the inability to selectively disrupt these patterns of activity has hampered the precise definition of the function of these modes of signaling. Here, we addressed the role of phasic DA in learning and other DA-dependent behaviors by attenuating DA neuron burst firing and subsequent DA release, without altering tonic neural activity. Disruption of phasic DA was achieved by selective genetic inactivation of NMDA-type, ionotropic glutamate receptors in DA neurons. Disruption of phasic DA neuron activity impaired the acquisition of numerous conditioned behavioral responses, and dramatically attenuated learning about cues that predicted rewarding and aversive events while leaving many other DA-dependent behaviors unaffected.
Asunto(s)
Dopamina/fisiología , Aprendizaje , Mesencéfalo/fisiología , Neuronas/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Animales , Atención , Conducta , Dopamina/metabolismo , Ingestión de Líquidos , Miedo , Aprendizaje por Laberinto , Mesencéfalo/citología , Mesencéfalo/metabolismo , Ratones , Ratones Noqueados , Neuronas/metabolismo , Receptores de N-Metil-D-Aspartato/genética , RecompensaRESUMEN
Two-way active avoidance (2WAA) involves learning Pavlovian (association of a sound cue with a foot shock) and instrumental (shock avoidance) contingencies. To identify regions where dopamine (DA) is involved in mediating 2WAA, we restored DA signaling in specific brain areas of dopamine-deficient (DD) mice by local reactivation of conditionally inactivated Th genes using viral gene therapy. Among all targeted areas--prefrontal cortex (PFC), amygdala, ventral striatum, dorsal striatum, and whole striatum--only restoration of DA signaling to both the whole striatum together with the amygdala enabled DD mice to acquire 2WAA. However, after prolonged overtraining during which DD mice had DA synthesis systemically reconstituted pharmacologically with L-3,4-dihydroxyphenylalanine (L-Dopa), DA signaling in the striatum alone was sufficient to maintain 2WAA, whereas DA signaling in the PFC together with the amygdala was insufficient to maintain 2WAA. Our results indicate that learning 2WAA requires DA signaling in both the amygdala and the entire striatum; however, after sufficient training, DA signaling in the striatum alone can maintain the learned avoidance behavior.
Asunto(s)
Amígdala del Cerebelo/fisiología , Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Cuerpo Estriado/fisiología , Dopamina/metabolismo , Transducción de Señal/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Cafeína/farmacología , Caveolina 2/genética , Estimulantes del Sistema Nervioso Central/farmacología , Condicionamiento Clásico/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Dopaminérgicos/farmacología , Reacción de Fuga/efectos de los fármacos , Reacción de Fuga/fisiología , Miedo , Levodopa/farmacología , Ratones , Ratones Noqueados , Tiempo de Reacción/fisiología , Transducción de Señal/efectos de los fármacos , Tirosina 3-Monooxigenasa/deficiencia , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Emotions are time-varying internal states that promote survival in the face of dynamic environments and shifting homeostatic needs. Research in non-human organisms has recently afforded specific insights into the neural mechanisms that support the emergence, persistence, and decay of affective states. Concurrently, a separate affective neuroscience literature has begun to dissect the neural bases of affective dynamics in humans. However, the circuit-level mechanisms identified in animals lack a clear mapping to the human neuroscience literature. As a result, critical questions pertaining to the neural bases of affective dynamics in humans remain unanswered. To address these shortcomings, the present review integrates findings from humans and non-human organisms to highlight the neural mechanisms that govern the temporal features of emotional states. Using the theory of affective chronometry as an organizing framework, we describe the specific neural mechanisms and modulatory factors that arbitrate the rise-time, intensity, and duration of emotional states.
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Encéfalo , Neurociencias , Afecto , Animales , Mapeo Encefálico , Emociones , Humanos , Imagen por Resonancia Magnética , Modelos AnimalesRESUMEN
Patterned coordination of network activity in the basolateral amygdala (BLA) is important for fear expression. Neuromodulatory systems play an essential role in regulating changes between behavioral states, however the mechanisms underlying this neuromodulatory control of transitions between brain and behavioral states remain largely unknown. We show that chemogenetic Gq activation and α1 adrenoreceptor activation in mouse BLA parvalbumin (PV) interneurons induces a previously undescribed, stereotyped phasic bursting in PV neurons and time-locked synchronized bursts of inhibitory postsynaptic currents and phasic firing in BLA principal neurons. This Gq-coupled receptor activation in PV neurons suppresses gamma oscillations in vivo and in an ex vivo slice model, and facilitates fear memory recall, which is consistent with BLA gamma suppression during conditioned fear expression. Thus, here we identify a neuromodulatory mechanism in PV inhibitory interneurons of the BLA which regulates BLA network oscillations and fear memory recall.
Asunto(s)
Complejo Nuclear Basolateral , Parvalbúminas , Animales , Complejo Nuclear Basolateral/metabolismo , Miedo , Potenciales Postsinápticos Inhibidores/fisiología , Interneuronas/metabolismo , Ratones , Parvalbúminas/metabolismoRESUMEN
The neural circuits orchestrating complex behavioral response strategies to threat are not understood. In this issue of Neuron, Wang et al. (2021) establish the hypothalamic dorsal premammillary nucleus as a critical node that communicates with thalamic and midbrain regions to coordinate diverse escape strategies.
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Navegación Espacial , Hipotálamo , Mesencéfalo , Neuronas , TálamoRESUMEN
Discriminating dangerous predictive stimuli from non-threatening stimuli is vital for maintaining optimal behavioral strategies. A new study finds that novel stress-related peptide pathways to the dopaminergic midbrain play a fundamental role in threat generalization.
Asunto(s)
Miedo , Neurobiología , Generalización Psicológica , PéptidosRESUMEN
Fear- and anxiety-related behaviors significantly contribute to an organism's survival. However, exaggerated defensive responses to perceived threat are characteristic of various anxiety disorders, which are the most prevalent form of mental illness in the United States. Discovering the neurobiological mechanisms responsible for defensive behaviors will aid in the development of novel therapeutic interventions. Pavlovian fear conditioning is a widely used laboratory paradigm to study fear-related learning and memory. A major limitation of traditional Pavlovian fear conditioning paradigms is that freezing is the only defensive behavior monitored. We recently developed a modified Pavlovian fear conditioning paradigm that allows us to study both conditioned freezing and flight (also known as escape) behavior within individual subjects. This model employs higher intensity footshocks and a greater number of pairings between the conditioned stimulus and unconditioned stimulus. Additionally, this conditioned flight paradigm utilizes serial presentation of pure tone and white noise auditory stimuli as the conditioned stimulus. Following conditioning in this paradigm, mice exhibit freezing behavior in response to the tone stimulus, and flight responses during the white noise. This conditioning model can be applied to the study of rapid and flexible transitions between behavioral responses necessary for survival.
Asunto(s)
Conducta Animal , Condicionamiento Clásico/fisiología , Reacción de Fuga/fisiología , Miedo/fisiología , Reacción Cataléptica de Congelación/fisiología , Animales , Extinción Psicológica , Femenino , Congelación , Masculino , Memoria/fisiología , Ratones Endogámicos C57BL , Grabación en VideoRESUMEN
Dopamine (DA) is implicated in many behaviors, including motor function, cognition, and reward processing; however, the role of DA in fear processing remains equivocal. To examine the role of DA in fear-related learning, dopamine-deficient (DD) mice were tested in a fear-potentiated startle paradigm. DA synthesis can be restored in DD mice through administration of 3, 4-dihydroxy-l-phenylalanine (l-Dopa), thereby permitting the assessment of fear processing in either a DA-depleted or -replete state. Fear-potentiated startle was absent in DD mice but could be restored by l-Dopa administration immediately after fear conditioning. Selective viral-mediated restoration of DA synthesis within the ventral tegmental area fully restored fear learning in DD mice, and restoration of DA synthesis to DA neurons projecting to the basolateral amygdala restored short-term memory but not long-term memory or shock sensitization. We also demonstrate that the DA D(1) receptor (D(1)R) and D(2)-like receptors are necessary for cue-dependent fear learning. These findings indicate that DA acting on multiple receptor subtypes within multiple target regions facilitates the stabilization of fear memory.
Asunto(s)
Condicionamiento Psicológico/fisiología , Señales (Psicología) , Dopamina/fisiología , Miedo/fisiología , Animales , Dopamina/deficiencia , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Receptores Dopaminérgicos/deficiencia , Receptores Dopaminérgicos/fisiología , Reflejo de Sobresalto/fisiologíaRESUMEN
Females exhibit greater susceptibility to trauma- and stress-related disorders compared to males; therefore, it is imperative to study sex differences in the mode and magnitude of defensive responses in the face of threat. To test for sex differences in defensive behavior, we used a modified Pavlovian fear conditioning paradigm that elicits clear transitions between freezing and flight behaviors within individual subjects. Female mice subjected to this paradigm exhibited more freezing behavior compared to males, especially during the intertrial interval period. Female mice also exhibited more freezing in response to conditioned auditory stimuli in the last block of extinction training. Furthermore, there were sex differences in the expression of other adaptive behaviors during fear conditioning. Assaying rearing, grooming, and tail rattling behaviors during the conditioned flight paradigm yielded measurable differences across sessions and between males and females. Overall, these results provide insight into sex-dependent alterations in mouse behavior induced by fear conditioning.
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Reacción de Prevención , Condicionamiento Clásico , Miedo , Caracteres Sexuales , Animales , Conducta Animal , Extinción Psicológica , Femenino , Aseo Animal , Masculino , Ratones Endogámicos C57BLRESUMEN
The central nucleus of the amygdala (CEA) is a striatum-like structure orchestrating a diverse set of adaptive behaviors, including defensive and appetitive responses [1-3]. Studies using anatomical, electrophysiological, imaging and optogenetic approaches revealed that the CEA network consists of recurrent inhibitory circuits comprised of precisely connected functionally and genetically defined cell types that can select and control specific behavioral outputs [3,4,5â¢,6â¢,7-9,11,12]. While bivalent functionality of the CEA in adaptive behavior has been clearly demonstrated, we are just beginning to understand to which degree individual CEA circuit elements are functionally segregated or overlapping. Importantly, recent studies seem to suggest that optogenetic manipulations of the same, or overlapping cell populations can give rise to distinct, or sometimes even opposite, behavioral phenotypes [5â¢,6â¢,9-12]. In this review, we discuss recent progress in our understanding of how defined CEA circuits can control defensive and appetitive behaviors, and how seemingly contradictory results could point to an integrated concept of CEA function.