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Ventral pallidum neurons are necessary to generalize and express fear-related responding in a minimal threat setting
Fear generalization is a hallmark of anxiety disorders. Experimentally, fear generalization can 29 be difficult to dissociate from its counterpart, fear discrimination. Here we use minimal threat 30 learning procedures to reveal such a dissociation. We show that in Long Evans rats, an auditory 31 threat cue predicting foot shock on 10% of trials produces a discriminated fear response that 32 does not generalize to a neutral auditory cue. Even slightly higher foot shock probabilities (30% 33 and 20%) produce fear generalization. AAV-mediated, caspase-3 deletion of ventral pallidum 34 neurons abolishes fear generalization and reduces threat cue responding during extinction. The 35 ventral pallidum’s contribution to fear generalization and extinction threat responding does not 36 depend on inputs from the nucleus accumbens. The results demonstrate a minimal threat 37 learning approach to dissociate fear discrimination from fear generalization, and a novel role for 38 the ventral pallidum in generalizing and expressing fear.
Ethograms reveal a fear conditioned visual cue to organize diverse behaviors
Recognizing and responding to threat cues is essential to survival. In rats, freezing is the most common behavior measured. Previously we demonstrated a threat cue can organize diverse behaviors (Chu et al., 2024). However, the experimental design of Chu et al. (2024) was complex and the findings descriptive. Here, we gave female and male Long Evans rats simple paired or unpaired presentations of a light and foot shock (8 total) in a conditioned suppression setting, using a range of shock intensities (0.15, 0.25, 0.35 or 0.5 mA). We found that conditioned suppression was only observed at higher foot shock intensities (0.35 mA and 0.5 mA). We constructed comprehensive, temporal ethograms by scoring 22,272 frames of behavior for 12 mutually exclusive behavior categories in 200 ms intervals around cue presentation. A 0.5 mA and 0.35 mA shock-paired visual cue suppressed reward seeking, rearing and scaling, as well as light-directed rearing and light-directed scaling. The shock-paired visual paired cue further elicited locomotion and freezing. Linear discriminant analyses showed that ethogram data could accurately classify rats into paired and unpaired groups. Considering the complete ethogram data produced superior classification than considering subsets of behaviors. The results demonstrate diverse threat-elicited behaviors – in a simple Pavlovian fear conditioning design – containing sufficient information to distinguish the fear learning status of individual rats.
A fear conditioned cue orchestrates a suite of behaviors in rats
Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that – in addition to jumping, and rearing – is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of dangerspecific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing – all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveals a fear conditioned cue to orchestrate a temporally organized suite of behaviors.
2023
McDannald MA (2023). "Pavlovian fear condtioning is more than you think it is." Journal of Neuroscience. [pdf]
Wright KM, Cieslewski, Chu A, McDannald MA (2023). "Optogenetic inhibition of the caudal substantia nigra inflates behavioral responding to uncertain threat and safety." Behavioral Neuroscience. [pdf]
Wright KM, Kantor CE, Moaddab M, McDannald MA (2023). "Timing of behavioral responding to long duration Pavlovian fear conditioned cues." bioRxiv. [pdf]
2022
Strickland JS and McDannald MA (2022). "Brainstem networks construct threat probability and prediction error from neuronal building blocks." Nature Communications. [pdf]
Walker RA, Suthard RL, Perison TN, Sheehan NM, Dwyer CC, Lee JK, Enabulele EK, Ray MH and McDannald MA (2022). "Dorsal Raphe 5-HT Neurons Utilize, But Do Not Generate, Negative Aversive Prediction Errors." eNeuro. [pdf]
Ray MH, Moaddab M and McDannald MA (2022). "Threat and bidirectional valence signaling in the nucleus accumbens core." Journal of Neuroscience. [pdf]
2021
McDannald MA (2021). "Decision making: Serotonin goes for goal." Current Biology. [pdf]
Moaddab M and McDannald MA (2021). "Retrorubral field is a hub for diverse threat and aversive outcome signals." Current Biology. [pdf]
Moaddab M, Ray MH and McDannald MA (2021). "Ventral pallidum neurons dynamically signal relative threat." Communications Biology. [pdf]
Strickland JA, Dileo AD, Moaddab M, Ray MH, Walker RA, Wright KW and McDannald MA (2021). "Foot shock facilitates reward seeking in an experience-dependent manner." Behavioural Brain Research. [pdf]
2020
Moaddab M, Wright KW and McDannald MA (2020). "Early adolescent adversity alters periaqueductal gray/dorsal raphe threat responding in adult female rats." Scientific Reports. [pdf]
Ray MH, Russ AN, Walker RA and McDannald MA (2020). "The nucleus accumbens core is necessary to scale fear to degree of threat." Journal of Neuroscience. [pdf]