ePoster

Periaqueductal Gray Neurons are All-or-none Threat Gates Modulated by Escape Experience

Yaara Lefler, Alex Fudge, Yeqing Wang, Goncalo Ferreira, Tiago Branco
COSYNE 2025(2025)
Montreal, Canada

Conference

COSYNE 2025

Montreal, Canada

Resources

Authors & Affiliations

Yaara Lefler, Alex Fudge, Yeqing Wang, Goncalo Ferreira, Tiago Branco

Abstract

When confronted with immediate threats, selecting the appropriate behavior at the right moment is essential for survival. Animals must constantly process information from the environment to accurately identify potential danger and respond by escaping to safety. While escape is largely instinctive, it is also adaptable, allowing animals to adjust to changing environmental conditions and internal states. The superior colliculus and dorsal periaqueductal gray (dPAG) play a crucial role in the neural circuitry responsible for processing threatening cues and triggering escape responses. However, the mechanisms by which sensory inputs are integrated to signal threat, and how neuronal processes control the decision and flexibility of escape, are largely unknown. To explore this, we conducted whole-cell patch-clamp recordings from dPAG neurons in mice exposed to threatening stimuli that cause escape-to-shelter responses. Our findings reveal that dPAG neurons are highly excitable, requiring only a small number of synaptic inputs to reach the action potential threshold. These neurons respond robustly to threatening stimuli, regardless of the stimulus type, with the intensity of the response correlating with the likelihood of escape, suggesting that the dPAG acts as an all-or-none threat gate. In a subset of dPAG neurons, repeated exposure to threats leads to a sustained subthreshold depolarization, likely caused by a local disinhibitory mechanism. This depolarization, lasting several minutes, reduces the amount of input needed to trigger action potentials, making subsequent threats more likely to evoke escape responses, poising the dPAG as a key center for modulating threat sensitivity. Our results suggest a cellular mechanism for gating threats and modulating instinctive escape behavior. This biophysical process, at the level of individual midbrain neurons, could potentially serve as a general mechanism for controlling and adapting behavioral responses in dynamic environments.

Unique ID: cosyne-25/periaqueductal-gray-neurons-all-or-none-5b648086