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1.
Cell ; 173(6): 1329-1342.e18, 2018 05 31.
Article in English | MEDLINE | ID: mdl-29731170

ABSTRACT

Observational learning is a powerful survival tool allowing individuals to learn about threat-predictive stimuli without directly experiencing the pairing of the predictive cue and punishment. This ability has been linked to the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA). To investigate how information is encoded and transmitted through this circuit, we performed electrophysiological recordings in mice observing a demonstrator mouse undergo associative fear conditioning and found that BLA-projecting ACC (ACC→BLA) neurons preferentially encode socially derived aversive cue information. Inhibition of ACC→BLA alters real-time amygdala representation of the aversive cue during observational conditioning. Selective inhibition of the ACC→BLA projection impaired acquisition, but not expression, of observational fear conditioning. We show that information derived from observation about the aversive value of the cue is transmitted from the ACC to the BLA and that this routing of information is critically instructive for observational fear conditioning. VIDEO ABSTRACT.


Subject(s)
Basolateral Nuclear Complex/physiology , Cerebral Cortex/physiology , Learning/physiology , Amygdala/physiology , Animals , Behavior, Animal , Conditioning, Classical , Electrophysiological Phenomena , Fear , Light , Male , Memory/physiology , Mice , Neural Pathways/physiology , Neurons/physiology , Optogenetics , Prefrontal Cortex/physiology
2.
Nat Neurosci ; 20(6): 824-835, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28436980

ABSTRACT

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.


Subject(s)
Amygdala/physiology , Prefrontal Cortex/physiology , Punishment , Reward , 2-Amino-5-phosphonovalerate/administration & dosage , 2-Amino-5-phosphonovalerate/pharmacology , Action Potentials/physiology , Animals , Conditioning, Classical/drug effects , Conditioning, Classical/physiology , Cues , Discrimination, Psychological/drug effects , Discrimination, Psychological/physiology , Electric Stimulation , Immobility Response, Tonic/physiology , Male , Microinjections , Neural Inhibition/physiology , Neural Pathways/physiology , Prefrontal Cortex/drug effects , Quinoxalines/administration & dosage , Quinoxalines/pharmacology , Rats , Rats, Transgenic , Sucrose
3.
Neuron ; 90(6): 1286-1298, 2016 06 15.
Article in English | MEDLINE | ID: mdl-27238864

ABSTRACT

Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic component of the LH-VTA pathway supports positive reinforcement and place preference, while the glutamatergic component mediates place avoidance. In addition, our results indicate that photoactivation of these projections modulates other behaviors, such as social interaction and perseverant investigation of a novel object. We provide evidence that photostimulation of the GABAergic LH-VTA component, but not the glutamatergic component, increases dopamine (DA) release in the nucleus accumbens (NAc) via inhibition of local VTA GABAergic neurons. Our study clarifies how GABAergic LH inputs to the VTA can contribute to generalized behavioral activation across multiple contexts, consistent with a role in increasing motivational salience. VIDEO ABSTRACT.


Subject(s)
Behavior, Animal , Dopaminergic Neurons/physiology , Hypothalamic Area, Lateral/physiology , Neural Inhibition/physiology , Reward , Ventral Tegmental Area/physiology , Animals , Avoidance Learning/physiology , Dopamine/metabolism , GABAergic Neurons/physiology , Mice , Nucleus Accumbens/metabolism
4.
Cell ; 160(3): 528-41, 2015 Jan 29.
Article in English | MEDLINE | ID: mdl-25635460

ABSTRACT

The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to reward processing, but the computations within the LH-VTA loop that give rise to specific aspects of behavior have been difficult to isolate. We show that LH-VTA neurons encode the learned action of seeking a reward, independent of reward availability. In contrast, LH neurons downstream of VTA encode reward-predictive cues and unexpected reward omission. We show that inhibiting the LH-VTA pathway reduces "compulsive" sucrose seeking but not food consumption in hungry mice. We reveal that the LH sends excitatory and inhibitory input onto VTA dopamine (DA) and GABA neurons, and that the GABAergic projection drives feeding-related behavior. Our study overlays information about the type, function, and connectivity of LH neurons and identifies a neural circuit that selectively controls compulsive sugar consumption, without preventing feeding necessary for survival, providing a potential target for therapeutic interventions for compulsive-overeating disorder.


Subject(s)
Behavior, Animal , Hypothalamic Area, Lateral/physiology , Ventral Tegmental Area/physiology , Animals , Feedback , Hypothalamic Area, Lateral/cytology , Mice , Models, Neurological , Neural Pathways , Neurons/cytology , Reward , Sucrose , gamma-Aminobutyric Acid/metabolism
5.
Neuron ; 79(4): 658-64, 2013 Aug 21.
Article in English | MEDLINE | ID: mdl-23972595

ABSTRACT

The basolateral amygdala (BLA) and ventral hippocampus (vHPC) have both been implicated in mediating anxiety-related behaviors, but the functional contribution of BLA inputs to the vHPC has never been directly investigated. Here we show that activation of BLA-vHPC synapses acutely and robustly increased anxiety-related behaviors, while inhibition of BLA-vHPC synapses decreased anxiety-related behaviors. We combined optogenetic approaches with in vivo pharmacological manipulations and ex vivo whole-cell patch-clamp recordings to dissect the local circuit mechanisms, demonstrating that activation of BLA terminals in the vHPC provided monosynaptic, glutamatergic inputs to vHPC pyramidal neurons. Furthermore, BLA inputs exerted polysynaptic, inhibitory effects mediated by local interneurons in the vHPC that may serve to balance the circuit locally. These data establish a role for BLA-vHPC synapses in bidirectionally controlling anxiety-related behaviors in an immediate, yet reversible, manner and a model for the local circuit mechanism of BLA inputs in the vHPC.


Subject(s)
Amygdala/physiopathology , Anxiety/pathology , Hippocampus/physiopathology , Neural Pathways/physiology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Animals , Anxiety/genetics , Bacterial Proteins/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Channelrhodopsins , Disease Models, Animal , Excitatory Amino Acid Antagonists/pharmacology , Exploratory Behavior , Halorhodopsins/genetics , Halorhodopsins/metabolism , Hippocampus/cytology , In Vitro Techniques , Luminescent Proteins/genetics , Male , Maze Learning , Membrane Potentials/genetics , Membrane Potentials/physiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neurons/physiology , Sodium Channel Blockers/pharmacology , Synapses/physiology , Tetrodotoxin/pharmacology , Valine/analogs & derivatives , Valine/pharmacology
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