title: Extrinsic Sources of Cholinergic Innervation of the Striatal Complex: A Whole-Brain Mapping Analysis.
abstract: Acetylcholine in the striatal complex plays an important role in normal behavior and is affected in a number of neurological disorders. Although early studies suggested that acetylcholine in the striatum (STR) is derived almost exclusively from cholinergic interneurons (CIN), recent axonal mapping studies using conditional anterograde tracing have revealed the existence of a prominent direct cholinergic pathway from the pedunculopontine and laterodorsal tegmental nuclei to the dorsal striatum and nucleus accumbens. The identification of the importance of this pathway is essential for creating a complete model of cholinergic modulation in the striatum, and it opens the question as to whether other populations of cholinergic neurons may also contribute to such modulation. Here, using novel viral tracing technologies based on phenotype-specific fluorescent reporter expression in combination with retrograde tracing, we aimed to define other sources of cholinergic innervation of the striatum. Systematic mapping of the projections of all cholinergic structures in the brain (Ch1 to Ch8) by means of conditional tracing of cholinergic axons, revealed that the only extrinsic source of cholinergic innervation arises in the brainstem pedunculopontine and laterodorsal tegmental nuclei. Our results thus place the pedunculopontine and laterodorsal nuclei in a key and exclusive position to provide extrinsic cholinergic modulation of the activity of the striatal systems.
authors.affiliation: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of OxfordOxford, UK; Department of Neuroscience, Psychology and Behaviour, University of LeicesterLeicester, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dautan
authors.affiliation: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of OxfordOxford, UK; Department of Anatomy, School of Medicine, Marmara UniversityIstanbul, Turkey.
authors.forename: Husniye
authors.initials: H
authors.lastname: Hacioğlu Bay
authors.affiliation: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford Oxford, UK.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Bolam
authors.affiliation: Department of Neuroscience, Psychology and Behaviour, University of Leicester Leicester, UK.
authors.forename: Todor V
authors.initials: TV
authors.lastname: Gerdjikov
authors.affiliation: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of OxfordOxford, UK; Center for Molecular and Behavioral Neuroscience, Rutgers UniversityNewark, NJ, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Mena-Segovia
keywords: acetylcholine; cholinergic brainstem; cholinergic interneurons; nucleus accumbens; striatum
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