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Published on: November 8, 2024
Chronic alcohol consumption and abstinence disrupt cholinergic gene expression in the mesopontine tegmentum of
Shivani P Vaidya1, Daisy L Spark1, Leigh C Walker1
1The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
Abstract:
The mesopontine tegmentum (MPT), consisting of the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) regulates reward and aversion via direct projections to key regions including the striatum, substantia nigra, and ventral tegmental area. Chronic alcohol consumption followed by abstinence significantly downregulates the M4 muscarinic receptor in the dorsolateral striatum. Since cholinergic projections from the mesopontine tegmentum (MPT) provide an external source of acetylcholine to this region, it is imperative to investigate how alcohol exposure and subsequent abstinence induce molecular alterations within the cholinergic system of the mesopontine tegmentum. In this study, we first characterised PPTg and LDTg projections to the dorsal striatum in alcohol-preferring iP rats, then assessed changes to cholinergic gene expression in the MPT following long-term voluntary alcohol consumption and abstinence. Using a combined retrograde tracing and immunofluorescence approach, we demonstrate that PPTg and LDTg provide direct, bilateral cholinergic innervation to both the dorsolateral and dorsomedial striatum, with less topographical specificity than previously reported in other strains. Following six months of intermittent alcohol access, RT-qPCR revealed a transient decrease in Chrna7 expression in the LDTg that returned to baseline after 14 days abstinence, and a downregulation of Chrm4 expression in the PPTg during abstinence. Together, these findings reveal that long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD. SIGNIFICANCE STATEMENT: Long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD.
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