期刊
PROGRESS IN NEUROBIOLOGY
卷 185, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2019.101734
关键词
Prepulse inhibition; Sensorimotor gating; Cholinergic; Pedunculopontine tegmental nucleus; DREADDs; Neurocircuitry; Startle
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- NSERC Postgraduate Scholarship-Doctoral [PGSD3-5193082018]
- Jonathan & Joshua Memorial Graduate Scholarship
Prepulse inhibition (PPI) is an operational measure of sensorimotor gating. Deficits of PPI are a hallmark of schizophrenia and associated with several other psychiatric illnesses such as e.g. autism spectrum disorder, yet the mechanisms underlying PPI are still not fully understood. There is growing evidence contradicting the long-standing hypothesis that PPI is mediated by a short feed-forward midbrain circuitry including inhibitory cholinergic projections from the pedunculopontine tegmental nucleus (PPTg) to the startle pathway. Here, we employed a chemogenetic approach to explore the involvement of the PPTg in general, and cholinergic neurons specifically, in PPI. Activation of inhibitory DREADDs (designer receptors exclusively activated by designer drugs) in the PPTg by systemic administration of clozapine-N-oxide (CNO) disrupted PPI, confirming the involvement of the PPTg in PPI. In contrast, chemogenetic inhibition of specifically cholinergic PPTg neurons had no effect on PPI, but inhibited morphine-induced conditioned place preference (CPP) in the same animals, showing that the DREADDs were effective in modulating behavior. These findings support a functional role of the PPTg and/or neighboring structures in PPI in accordance with previous lesion studies, but also provide strong evidence against the hypothesis that specifically cholinergic PPTg neurons are involved in mediating PPI, implicating rather non-cholinergic midbrain neurons.
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