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 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.