Biology subjects

McDannald, M. A.

Publications and source records attributed to McDannald, M. A..

7 recordsLinked to original sources

bioRxiv2024

Ethograms reveal a fear conditioned visual cue to organize diverse behaviors in rats

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.

neuroscience↗

bioRxiv2023

Optogenetic inhibition of the caudal substantia nigra inflates behavioral responding to uncertain threat and safety

Defensive responding is adaptive when it approximates current threat, but maladaptive when it exceeds current threat. Here we asked if the substantia nigra, a region consistently implicated in reward, is necessary to show appropriate levels of defensive responding in Pavlovian fear discrimination. Rats received bilateral transduction of the caudal substantia nigra with halorhodopsin or a control fluorophore, and bilateral ferrule implants. Rats then behaviorally discriminated cues predicting unique foot shock probabilities (danger, p=1; uncertainty, p=0.25; and safety, p=0). Green-light illumination (532 nm) during cue presentation inflated defensive responding of halorhodopsin rats - measured by suppression of reward seeking - to uncertainty and safety beyond control levels. Green-light illumination outside of cue presentation had no impact on halorhodopsin or control rat responding. The results reveal caudal substantia nigra cue activity is necessary to inhibit defensive responding to non-threatening and uncertain threat cues.

neuroscience↗

bioRxiv2023

Timing of behavioral responding to long-duration Pavlovian fear conditioned cues

Behavioral responding is most beneficial when it reflects event timing. Compared to reward, there are fewer studies on timing of defensive responding. We gave female and male rats Pavlovian fear conditioning over a baseline of reward seeking. Two 100-s cues predicted foot shock at different time points. Rats acquired timing of behavioral responding to both cues. Suppression of reward seeking was minimal at cue onset and maximal before shock delivery. Rats also came to minimize suppression of reward seeking following cue offset. The results reveal timing as a mechanism to focus defensive responding to shock-imminent, cue periods.

neuroscience↗

bioRxiv2022

A fear conditioned cue orchestrates a suite of behaviors

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 24 rats (12 female) Pavlovian fear discrimination over a baseline of reward seeking. The within-subjects procedure had full controls for associative learning, consisting of three cues predicting unique foot shock probabilities: danger (p=1), uncertainty (p=0.25), and safety (p=0). TTL-triggered cameras captured 5 behavior frames/s prior to and during cue presentation. We scored 86,400 frames for nine discrete behaviors spanning reward, passive fear, and active fear. Temporal ethograms show that a fear conditioned cue elicits locomotion, jumping, and rearing that is maximal towards cue offset, when foot shock is imminent. A fear conditioned cue further suppresses reward-related behavior, and elicits freezing in a sex-specific manner. The differing temporal profiles and independent expression of these behaviors reveal a fear conditioned cue to orchestrate a rich and intricate suite of behaviors.

animal behavior and cognition↗

bioRxiv2021

Distinct threat and valence signals in rat nucleus accumbens core

Appropriate responding to threat and reward is essential to survival. The nucleus accumbens core (NAcc) is known to support and organize reward behavior. More recently our laboratory has shown the NAcc is necessary to discriminate cues for threat and safety. To directly reveal NAcc threat responding, we recorded single-unit activity from 7 female rats undergoing Pavlovian fear discrimination. Rats fully discriminated cues for danger, uncertainty, and safety. Demonstrating direct threat responding, most NAcc neurons showed greatest firing changes to danger and uncertainty. Heterogeneity in cue and reward firing led to the detection of multiple, functional populations. One NAcc population specifically decreased firing to threat (danger and uncertainty). A separate population bi-directionally signaled valence through firing decreases to negative valence events (danger and uncertainty) and opposing firing increases to positive valence events (reward and safety onset). The findings point to the NAcc as a neural source of threat information and a more general valence hub.

neuroscience↗

bioRxiv2020

Ventral pallidum neurons signal relative threat

Ventral pallidum (VP) neurons scale firing increases to reward value and decrease firing to aversive cues. Anatomical connectivity suggests a critical role for the VP in threat-related behavior. Here we tested whether firing decreases in VP neurons conform to relative threat by recording single units while male rats discriminated cues predicting unique foot shock probabilities. Rats behavior and VP single unit firing discriminated danger, uncertainty and safety cues. We found that two VP populations (Low firing and Intermediate firing) signaled relative threat, proportionally decreased firing according shock probability: danger < uncertainty < safety. Low firing neurons showed reward firing increases, consistent with a general signal for relative value. Intermediate firing neurons were unresponsive to reward, revealing a specific signal for relative threat. The results suggest an integral role for the VP in threat-related behavior.

neuroscience↗

bioRxiv2020

The nucleus accumbens core is necessary to scale fear to degree of threat

Fear is adaptive when the level of the response rapidly scales to degree of threat. Using a discrimination procedure consisting of danger, uncertainty and safety cues, we have found rapid fear scaling (within two seconds of cue presentation) in male rats. Here we examined a possible role for the nucleus accumbens core (NAcc) in the acquisition and expression of fear scaling. In experiment 1, male Long Evans rats received bilateral sham or neurotoxic NAcc lesions, recovered and underwent fear discrimination. NAcc-lesioned rats were generally impaired in scaling fear to degree of threat, and specifically impaired in rapid uncertainty-safety discrimination. In experiment 2, male Long Evans rats received NAcc transduction with halorhodopsin or a control fluorophore. After fear scaling was established, the NAcc was illuminated during cue or control periods. NAcc-halorhodopsin rats receiving cue illumination were specifically impaired in rapid uncertainty-safety discrimination. The results reveal a general role for the NAcc in scaling fear to degree of threat, and a specific role in rapid discrimination of uncertain threat and safety. Significance StatementRapidly discriminating cues for threat and safety is essential for survival and impaired threat-safety discrimination is a hallmark of stress and anxiety disorders. In two experiments, we induced nucleus accumbens core (NAcc) dysfunction in rats receiving fear discrimination consisting of cues for danger, uncertainty and safety. Permanent NAcc dysfunction, via neurotoxic lesion, generally disrupted the ability to scale fear to degree of threat, and specifically impaired one component of scaling: rapid discrimination of uncertain threat and safety. Reversible NAcc dysfunction, via optogenetic inhibition, specifically impaired rapid discrimination of uncertain threat and safety. The results reveal that the NAcc is essential to scale fear to degree of threat, and is a plausible source of dysfunction in stress and anxiety disorders.

neuroscience↗