Retrograde labeling of neurons in the brain stem following injections of [3H]choline into the forebrain of the rat

Summary In an attempt to identify cholinergic neurons of the brain stem which project to the forebrain, retrograde labeling of neurons in the brain stem was examined by autoradiography following injections of 20 Ci ³H]choline into the thalamus, hypothalamus, basal forebrain and frontal cortex. After injections into the thalamus, retrogradely labeled neurons were evident within the lateral caudal mesencephalic and dorsolateral oral pontine tegmentum (particularly in the laterodorsal and pedunculopontine tegmental nuclei) and in smaller number within the latero-medial caudal pontine (Reticularis pontis caudalis, Rpc) and medullary (Reticularis gigantocellularis, Rgc) reticular formation. Following ³H]choline injections into the lateral hypothalamus and into the basal forebrain, retrogradely labeled neurons were localized in the dorsolateral caudal midbrain and oral pontine tegmentum and in smaller number in the medial medullary reticular formation (Rgc), as well as in the midbrain, pontine and medullary raphe nuclei. After injections into the anterior medial frontal cortex, a small number of retrogradely labeled cells were found in the brain stem within the laterodorsal tegmental nucleus and the dorsal raphe nucleus. In a parallel immunohistochemical study, choline acetyltransferase (ChAT)-positive neurons were found to be located in most of the regions of the reticular formation where cells were retrogradely labeled from the forebrain following ³H]choline injections. These results suggest that multiple cholinergic neurons within the lateral caudal midbrain and dorsolateral oral pontine tegmentum and a few within the caudal pontine and medullary reticular formation project to the thalamus, hypothalamus and basal forebrain and that a limited number of pontine cholinergic neurons project to the frontal cortex.Abbreviations of Neuroanatomical Terms 3 oculomotor nuc - 4 trochlear nuc - 4V fourth ventricle - 6 abducens nuc - 7 facial nuc - 7n facial nerve - 8n vestibulocochlear nerve - 10 dorsal motor nuc vagus - 12 hypoglossal nuc - 12n hypoglossal nerve - Amb ambiguus nuc - Aq cerebral aqueduct - bic brachium inf colliculus - CB cerebellum - CG central gray - CLi caudal linear nuc raphe - Cnf cuneiform nuc - cp cerebral peduncle - Cu cuneate nuc - D nuc Darkschewitsch - DCo dorsal cochlear nuc - DLL dorsal nuc lateral lemniscus - DPB dorsal parabrachial nuc - DR dorsal raphe nuc - dsc dorsal spinocerebellar tract - DTg dorsal tegmental nuc - dtgx dorsal tegmental decussation - ECu external cuneate nuc - Fl flocculus - IC inferior colliculus - icp inferior cerebellar peduncle - IF interfascicular nuc - InC interstitial nuc Cajal - IO inferior olive - IP interpeduncular nuc - KF Kolliker-Fuse nuc - LC locus coeruleus - Ldt laterodorsal tegmental nuc - Ifp longitudinal fasciculus pons - ll lateral lemniscus - LRt lateral reticular nuc - LRtS5 lateral reticular nucsubtrigeminal - LSO lateral superior olive - LTz lateral nuctrapezoid body - LVe lateral vestibular nuc - mcp middle cerebellar peduncle - Me5 mesencephalic trigeminal nuc - MGD medial geniculate nuc, dorsal - ml medial lemniscus - mlf medial longitudinal fasciculus - MnR median raphe nuc - Mo5 motor trigeminal nuc - MSO medial superior olive - MTz medial nuc trapezoid bbody - MVe medial vestibular nuc - PBg parabigeminal nuc - Pgl nuc paragigantocellularis lateralis - Pn pontine nuc - PPTg pedunculopontine tegmental nuc - Pr5 principal sensory trigeminal - PrH prepositive hypoglossal nuc - py pyramidal tract - Rgc reticularis gigantocellularis - Rgca reticularis gigantocellularis pars alpha - Rmes reticularis mesencephali - RMg raphe magnus nuc - RN red nuc - Ro nuc Roller - ROb raphe obscurus nuc - Rp reticularis parvicellularis - RPa raphe pallidus nuc - Rpc reticularis ponds caudalis - RPn raphe pontis nuc - Rpo reticularis pontis oralis - RR retrorubral nuc - rs rubrospinal tract - RtTg reticulotegmental nuc pons - s5 sensory root trigeminal nerve - SC superior colliculus - SCD superior colliculus,deep layer - SCI superior colliculus, intermediate layer - scp superior cerebellar peduncle - SCS superior colliculus, superficial layer - SGe suprageniculate nuc pons - SNC substantia nigra compact - SNL substantia nigra,lateral - SNR substantia nigra, reticular - SolL solitary tract nuc,lateral - SolM solitary tract nuc, medial - sp5 spinal tract trigeminal nerve - sp5I spinal trigeminal nuc, interpositus - Sp5O spinal trigeminal nuc, oral - spth spinothalamic tract - SpVe spinal vestibular nuc - SuVe superior vestibular nuc - tp tectopontine - ts tectospinal tract - tz trapezoid body - VCo ventral cochlear nuc - VLL ventral nuc lateral lemniscus - VPB ventral parabrachial nuc - vsc ventral spinocerebellar tract - VTA ventral tegmental area - VTg ventral tegmental nuc - vtgx ventral tegmental decussation - xscp decussation superior cerebellar peduncle This investigation was supported by grants from the Medical Research Council (MRC) of Canada (MT-6464: BEJ and MT 7376: AB). B.E. Jones holds a Chercheur Boursier Senior Award from the Fonds de la Recherche en Santé du Quebec (FRSQ), and A. Beaudet a Scientist Award from MRC