Biology subjects

Le, Q.-S. E.

Publications and source records attributed to Le, Q.-S. E..

3 recordsLinked to original sources

bioRxiv2023

Contributions of associative and non-associative learning to the dynamics of defensive ethograms

Defensive behavior changes based on threat intensity, proximity, and context of exposure, and learning about danger-predicting stimuli is critical for survival. However, most Pavlovian fear conditioning paradigms focus only on freezing behavior, obscuring the contributions of associative and non-associative mechanisms to dynamic defensive responses. To thoroughly investigate defensive ethograms, we subjected male and female adult C57BL/6J mice to a Pavlovian conditioning paradigm that paired footshock with a serial compound stimulus (SCS) consisting of distinct tone and white noise (WN) stimulus periods. To investigate how associative and non-associative mechanisms affect defensive responses, we compared this paired SCS-footshock group with four control groups that were conditioned with either pseudorandom unpaired presentations of SCS and footshock, shock only, or reversed SCS presentations with inverted tone--WN order, with paired or unpaired presentations. On day 2 of conditioning, the paired group exhibited robust freezing during the tone period with switching to explosive jumping and darting behaviors during the WN period. Comparatively, the unpaired and both reverse SCS groups expressed less tone-induced freezing and rarely showed jumping or darting during WN. Following the second day of conditioning, we observed how defensive behavior changed over two extinction sessions. During extinction, the tone-induced freezing decreased in the paired group and mice rapidly shifted from escape jumping during WN to a combination of freezing and darting. The unpaired, unpaired reverse, and shock-only groups displayed defensive tail rattling and darting during the SCS, with minimal freezing and jumping. Interestingly, the paired reverse group did not jump to WN, and tone-evoked freezing was resistant to extinction. These findings demonstrate that non-associative factors promote some defensive responsiveness, but associative factors are required for robust cue-induced freezing and high-intensity flight expression.

animal behavior and cognition↗

bioRxiv2022

Control of flight responses by a non-canonical corticolimbic pathway.

Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as posttraumatic stress and panic disorder.1 Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA)2; however, the source of neuronal excitation to 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. Using a behavioural paradigm that elicits both 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 projections target distinct medial CeA neuronal populations projecting to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.

neuroscience↗

bioRxiv2019

Sex Differences in Behavioral Responses during a Conditioned Flight Paradigm

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 higher percentages of freezing behavior compared to males, especially during the intertrial interval period. Female mice also exhibited more cued freezing in response to the conditioned 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. HighlightsO_LIMale and female mice do not differ in conditioned flight behavior. C_LIO_LIFemale mice exhibit more freezing behavior. C_LIO_LIRearing, self-grooming, and tail rattling behavior changes across days. C_LIO_LIMale mice exhibit more rearing and grooming behavior. C_LIO_LIFemale mice exhibit more tail rattling behavior. C_LI

animal behavior and cognition↗