Substance P in the ascending cholinergic reticular system

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Abstract
The neocortex receives a major cholinergic innervation from magnocellular neurones in the basal forebrain1–3. However, an ascending cholinergic reticular system has also been postulated to arise from acetylcholinesterase (AChE)-containing neurones in the midbrain and pontine tegmentum4–5. Lesions of this region decrease both AChE and choline acetyltransferase (ChAT) in various forebrain areas6,7, and recent immunohistochemical studies have identified a group of ChAT-containing cell bodies in the midbrain reticular formation and dorsolateral pontine tegmentum8,9. 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 forebrain11,12. 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.