Induction of flight via midbrain projections to the cuneiform nucleus

The dorsal periaqueductal gray is a midbrain structure implicated in the control of defensive behaviors and the processing of painful stimuli. Electrical stimulation or optogenetic activation of excitatory neurons in dorsal periaqueductal gray results in freezing or flight behavior at low or high intensity, respectively. However, the output structures that mediate these defensive behaviors remain unconfirmed. Here we carried out a targeted classification of neuron types in dorsal periaqueductal gray using multiplex in situ sequencing and then applied cell-type and projection-specific optogenetic stimulation to identify projections from dorsal periaqueductal gray to the cuneiform nucleus that promoted goal-directed flight behavior. These data confirmed that descending outputs from dorsal periaqueductal gray serve as a trigger for directed escape behavior.

Cardiovascular Effect of Dorsal Periaqueductal Gray During LPS- Induced Hypotension

Introduction: The central mechanism responsible for cardiovascular response to lipopolysaccharide (LPS) - induced hypotension is not completely determined and it is suggested numerous brain areas such as dorsal periaqueductal gray (dPAG) are involved. In this study the cardiovascular effect of the dPAG during LPS-induced hypotension was evaluated. Methods: Twenty male Wistar rats divided into four groups including 1) Control (Saline microinjected into dPAG), 2) Lidocaine 2%, 3) LPS (intravenously injected), and 4) Lidocaine + LPS were used. Catheterization of the femoral artery and vein was performed for the recording of blood pressure and LPS injection, respectively. Saline and lidocaine were microinjected into the dPAG nucleus then, LPS injection was done. Cardiovascular responses throughout of experiments were recorded and changes (∆) of systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were calculated over time and was compared with those control and LPS groups, using repeated measures ANOVA. Results: LPS significantly reduced ∆SBP and ∆MAP (P<0.05) and did not change the ∆HR than the control group. Lidocaine did not significantly affect basic ∆SBP, ∆MAP and ∆HR compared to the control. Injection of lidocaine before LPS significantly attenuated reduction of ∆SBP and ∆MAP evoked by LPS (P<0.05). Conclusion: Our data showed that blockade of the dPAG by lidocaine significantly ameliorates the hypotension induced by LPS. It confirms involvement of the dPAG in cardiovascular regulation during LPS-induced hypotension.

Neural network involving medial orbitofrontal cortex and dorsal periaqueductal gray regulation in human alcohol abuse

Prompted by recent evidence of neural circuitry in rodent models, functional magnetic resonance imaging and functional connectivity analyses were conducted for a large adolescent population at two ages, together with alcohol abuse measures, to characterize a neural network that may underlie the onset of alcoholism. A network centered on the medial orbitofrontal cortex (mOFC), as well as including the dorsal periaqueductal gray (dPAG), central nucleus of the amygdala, and nucleus accumbens, was identified, consistent with the rodent models, with evidence of both inhibitory and excitatory coregulation by the mOFC over the dPAG. Furthermore, significant relationships were detected between raised baseline excitatory coregulation in this network and impulsivity measures, supporting a role for negative urgency in alcohol dependence.

Dorsal Periaqueductal gray ensembles represent approach and avoidance states

Animals must balance needs to approach threats for risk-assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threat-avoidance ensemble in mice that showed higher activity far from threats such as the open arms of the elevated plus maze and a live predator. These cells were also more active during threat-avoidance behaviors such as escape and freezing, even though these behaviors have antagonistic motor output. Conversely, the threat-approach ensemble was more active during risk-assessment behaviors and near threats. Furthermore, unsupervised methods showed approach/avoidance states were encoded with shared activity patterns across threats. Lastly, the relative number of cells in each ensemble predicted threat-avoidance across mice. Thus, dPAG ensembles dynamically encode threat approach and avoidance states, providing a flexible mechanism to balance risk-assessment and danger avoidance.