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 (ACCâBLA) neurons preferentially encode socially derived aversive cue information. Inhibition of ACCâBLA alters real-time amygdala representation of the aversive cue during observational conditioning. Selective inhibition of the ACCâBLA 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/physiologyABSTRACT
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 BLAâPL 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 BLAâPL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLAâPL 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 , SucroseABSTRACT
Triplex-forming oligonucleotides (TFOs) are capable of coordinating genome modification in a targeted, site-specific manner, causing mutagenesis or even coordinating homologous recombination events. Here, we describe the use of TFOs such as peptide nucleic acids for targeted genome modification. We discuss this method and its applications and describe protocols for TFO design, delivery, and evaluation of activity in vitro and in vivo.
