Loss of rostral brainstem cholinergic activity results in decreased ultrasonic vocalization behavior and altered...

The parabigeminal (PBG), pedunculopontine (PPTg), and laterodorsal tegmental (LDTg) nuclei located in the rostral brainstem are the primary sources of the neurotransmitter acetylcholine (ACh) for the midbrain and thalamus, and as part of the ascending reticular activating system, these cholinergic signaling pathways regulate mouse behavioral responses to sensory stimuli. Here, I report that mice harboring a conditional deletion of ACh synthesis specifically within these nuclei (ChAT(En1 KO)) exhibit decreased ultrasonic vocalizations both as pups and adults, consistent with their previously reported hypoactivity when exploring the novel environment of the open field arena. Furthermore, in prepulse inhibition (PPI) tests, ChAT(En1 KO) animals exhibited increased sensorimotor gating in comparison to control littermates. These data suggest that ACh signaling arising from the rostral brainstem modulates animal behavior in part by tuning the levels of sensorimotor gating. Thus, the net effect of this cholinergic activity is to increase sensitivity to environmental stimuli, and loss of this pathway contributes to the hypoactivity in these mutants by raising the sensory threshold for eliciting exploratory behaviors.