Carroll, J. N. | Search bioRxiv

bioRxiv2025

Short-term synaptic dynamics in the ventrolateral and dorsomedial periaqueductal gray

The ability to assess and rapidly respond to predator threats in the environment is necessary for survival and requires dedicated neural circuits for threat detection, sensorimotor integration, and execution of ethologically appropriate behavioral responses. Although numerous brain circuits are involved in these processes, the midbrain periaqueductal gray (PAG) serves as an important central hub to generate ethologically appropriate passive and/or active defensive behaviors. Despite its central role in generating defensive behaviors, little is known about the intrinsic and synaptic properties of neurons across columns in the PAG. To address this knowledge gap, we made whole-cell voltage- and current-clamp recordings from unlabeled neurons in the vl- and dmPAG of mice. Consistent with in vivo work, our data highlights the relative importance of synaptic inhibition in both columns. Further, our results suggest that neurons in both the vl- and dmPAG prioritize frequency-invariant coding strategies, showing remarkably stable paired pulse ratios across interstimulus intervals. Despite this common theme, the underlying mechanism each column utilizes to achieve such frequency invariant coding is distinct, reflecting important differences in synaptic processing across columns. More specifically, while the vlPAG is relatively resistant to phasic short-term depression across stimulation frequencies, neurons in the dmPAG show a pronounced buildup of tonic/slow current during high frequency stimulation trains, which counteracts short-term depression of the phasic current amplitude observed during high frequency stimulation trains. This prolonged tonic current observed in the dmPAG prolongs the period of spike elevation, suggesting that high frequency stimulation may drive sustained activity in the dmPAG. Together, these results provide fundamental information of synaptic integration and network properties across columns in the PAG, which ultimately support their distinct roles in threat processing.

neuroscience↗

bioRxiv2024

Repeated presentation of visual threats drives innate fear habituation and is modulated by environmental and physiological factors

To survive predation, animals must be able to detect and appropriately respond to predator threats in their environment. Such defensive behaviors are thought to utilize hard-wired neural circuits for threat detection, sensorimotor integration, and execution of ethologically relevant behaviors. Despite being hard-wired, defensive behaviors (i.e. fear responses) are not fixed, but rather show remarkable flexibility, suggesting that extrinsic factors such as threat history, environmental contexts, and physiological state may alter innate defensive behavioral responses. The goal of the present study was to examine how extrinsic and intrinsic factors influence innate defensive behaviors in response to visual threats. In the absence of a protective shelter, our results indicate that mice showed robust freezing behavior following both looming (proximal) and sweeping (distal) threats, with increased behavioral vigor in response to looming stimuli, which represent a higher threat imminence. Repeated presentation of looming or sweeping stimuli at short inter-trial intervals resulted in robust habituation of freezing, which was accelerated at longer inter-trial intervals, regardless of contextual cues. Finally, physiological factors such as acute stress further disrupted innate freezing habituation, resulting in a delayed habituation phenotype, consistent with a heightened fear state. Together, our results indicate that extrinsic factors such as threat history, environmental familiarity, and physiological stressors have robust and diverse effects on defensive behaviors, highlighting the behavioral flexibility in how mice respond to predator threats.

animal behavior and cognition↗