Direct catecholaminergic-cholinergic interactions in the basal forebrain. I. Dopamine-?-hydroxylase- and tyrosine hydroxylase input to cholinergic neurons

Abstract

Immunocytochemical double-labeling techniques were used at the light and electron microscopic levels to investigate whether dopamine-beta-hydroxylase and tyrosine hydroxylase-containing axons contact basal forebrain cholinergic neurons. Dopamine-beta-hydroxylase- and tyrosine hydroxylase-positive fibers and terminals were found in close proximity to cholinergic neurons throughout extensive basal forebrain areas, including the vertical and horizontal limb of the diagonal band nuclei, the sublenticular substantia innominata, bed nucleus of the stria terminalis, ventral pallidum, and ventrolateral globus pallidus. Cholinergic cells in some aspects of the globus pallidus appeared to be contacted by tyrosine hydroxylase-positive but not dopamine-beta-hydroxylase-positive fibers, suggesting dopaminergic input to cholinergic neurons in these regions. Direct evidence for the termination of dopamine-beta-hydroxylase and tyrosine hydroxylase-positive fibers on cholinergic neurons was obtained in electron microscopic double-immunolabeling studies. Using high magnification light microscopic screening, both qualitative and quantitative differences were noted in the catecholaminergic innervation of forebrain cholinergic neurons. For example, while many cholinergic neurons were in close proximity to single dopamine-beta-hydroxylase-positive varicosities, others, particularly those located in the substantia innominatabed nucleus of the stria terminalis continuum, were apparently contacted by labeled fibers in repetitive fashion. The findings of the present study, together with our preliminary biochemical experiments (Zaborszky et al. [1993] Prog. Brain Res. 98:31-49) suggest that catecholaminergic afferents can differentially modulate forebrain cholinergic neurons. Such interactions may be important in learning and memory processes, and their perturbations may contribute to the cognitive decline seen in aging and in disorders such as Alzheimer's and Parkinson's diseases.

Dopamine Modulates Cholinergic Cortical Excitability in Alzheimer's Disease Patients

“…In fact pathological studies showed that in AD, in addition to b-amyloid and senile plaques deposits, changes in several neurotransmitter systems occur. Together with the cholinergic system, the serotoninergic and noradrenergic systems also seem to be strongly altered (Langlais et al, 1993;Nazarali and Reynolds, 1992;Reinikainen et al, 1988;Zaborszky and Cullinan, 1996). However, the dopaminergic is also implicated (Allard et al, 1994;McNeill et al, 1984).…”

Procholinergic and memory enhancing properties of the selective norepinephrine uptake inhibitor atomoxetine

“…Indeed, in the nucleus basalis, where the ACh neurons projecting to the cortex reside, DA and NE afferents have been shown to synapse on cholinergic somata. 21 The role of nucleus basalis D1-DA and a1-NE receptors in regulating cortical ACh release and in mediating the procholinergic effects of atomoxetine warrants further investigation.…”

Organization of the Basal Forebrain Cholinergic Projection System

“…Based on electron microscopic studies, BF cholinergic neurons receive ascending brainstem input from adrenaline containing neurons of the medulla (Hajszán and Zaborszky, 2002), from the locus coeruleus (Zaborszky et al, 1993), and from the dopaminergic substantia nigra/ventral tegmental area (Zaborszky and Cullinan, 1996;Gaykema and Zaborszky, 1996). Forebrain afferents synapsing with BF cholinergic neurons originate in various hypothalamic nuclei (Zaborszky and Cullinan, 1989;Cullinan and Zaborszky, 1991;Wu et al, 2004), the nucleus accumbens (Zaborszky and Cullinan, 1992) and the amygdala (Zaborszky et al, 1984;Paré and Smith, 1994;Jolkkonen et al, 2002).…”