Substance P in the ascending cholinergic reticular system

Abstract

The neocortex receives a major cholinergic innervation from magnocellular neurones in the basal forebrain^1–3. However, an ascending cholinergic reticular system has also been postulated to arise from acetylcholinesterase (AChE)-containing neurones in the midbrain and pontine tegmentum^4–5. Lesions of this region decrease both AChE and choline acetyltransferase (ChAT) in various forebrain areas^6,7, and recent immunohistochemical studies have identified a group of ChAT-containing cell bodies in the midbrain reticular formation and dorsolateral pontine tegmentum^8,9. Here we have combined retrograde tracing with ChAT immunohistochemistry to demonstrate that this tegmental cholinergic cell group also directly innervates the cerebral cortex. Other immunohistochemical studies have indicated that the neuropeptide substance P is also present in certain cells in the laterodorsal tegmentum¹⁰, and these too appear to project to the forebrain^11,12. We have therefore performed immunohistochemistry for both ChAT and substance P and have discovered that a subpopulation of the ascending cholinergic reticular neurones contains substance P. Thus, peptide–cholinergic coexistence, previously noted in peripheral neurones, also occurs in the brain.