Distribution of cholinergic, GABAergic and serotonergic neurons in the medial medullary reticular formation and their projections studied by cytotoxic lesions in the cat

As part of a larger study concerning the role of neurons in the medial medullary reticular formation in sleep-wake states, the distribution and projections of cholinergic, GABAergic and serotonergic neurons were studied within the lower brainstem of the cat. Cells were plotted with the aid of an image analysis system through the medullary reticular formation and raphe in adjacent sections immunostained for choline acetyltransferase, glutamic acid decarboxylase and serotonin. Immunostained fibres and varicosities were examined and quantified by microdensitometry in regions of the medulla, pons and upper spinal cord in normal and quisqualate-injected animals to assess the loss of local and distant projections following cytotoxic destruction of neurons in the medial medullary reticular formation. Choline acetyltransferase-immunoreactive neurons are unevenly and sparsely distributed, though none the less in significant numbers (estimated at approximately 9080 in total), through the medial medullary reticular formation, and are present in all tegmental fields, including the gigantocellular (approximately 3700) and magnocellular (approximately 1760) rostrally and the ventral (approximately 3240) and paramedian (approximately 380) caudally, and are absent in the midline raphe. Glutamic acid decarboxylase-immunoreactive neurons are more evenly and densely distributed in large numbers (estimated at approximately 18,720) through the medial medullary reticular formation, being present in the gigantocellular (approximately 5960), magnocellular (approximately 8260), ventral (approximately 2280) and paramedian (approximately 2220) tegmental fields, and are also numerous within the raphe magnus and pallidus-obscurus nuclei (approximately 3880). Serotonin-immunoreactive cells are sparse in the medial medullary reticular formation (estimated to total approximately 1540), where they are mainly located in the magnocellular tegmental field (approximately 1340), and are concentrated in larger numbers within the raphe nuclei (approximately 8060). Cholinergic varicose fibres were moderately densely distributed through the medial medullary reticular formation, as well as through more distant lateral, rostral and caudal brainstem and upper spinal regions. After cytotoxic lesions focussed in the gigantocellular and magnocellular tegmental fields, a loss of approximately 55% of the cholinergic neurons in the medial medullary reticular formation was associated with a minor decrease (approximately 35% in optical density measures) of local cholinergic fibres. Small and variable reductions in varicose fibres (and their optical density measures) were detected in distant structures (including the pontine lateral, gigantocellular and subcoerular tegmental fields and the caudal spinal trigeminal nucleus), that were none the less correlated with the number of intact medial medullary cholinergic cells, suggesting that these cells may project to distant brainstem targets, in addition to providing a minor proportion of the local cholinergic innervation of the medial medullary reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)