Localization of pre- and postsynaptic cholinergic markers in rodent forebrain: A brief history and comparison of rat and mouse

Rat and mouse models are widely used for studies in cognition and pathophysiology, among others. Here, we sought to determine to what extent these two model species differ for cholinergic and cholinoceptive features. For this purpose, we focused on cholinergic innervation patterns based on choline acetyltransferase (ChAT) immunostaining, and the expression of muscarinic acetylcholine receptors (mAChRs) detected immunocytochemically. In this brief review we first place cholinergic and cholinoceptive markers in a historic perspective, and then provide an overview of recent publications on cholinergic studies and techniques to provide a literature survey of current research. Next, we compare mouse (C57Bl/J6) and rat (Wistar) cholinergic and cholinoceptive systems simultaneously stained, respectively, for ChAT (analyzed qualitatively) and mAChRs (analyzed qualitatively and quantitatively). In general, the topographic cholinergic innervation patterns of both rodent species are highly comparable, with only considerable (but region specific) differences in number of detectable cholinergic interneurons, which are more numerous in rat. In contrast, immunolabeling for mAChRs, detected by the monoclonal antibody M35, differs markedly in the forebrain between the two species. In mouse brain, basal levels of activated and/or internalized mAChRs (as a consequence of cholinergic neurotransmission) are significantly higher. This suggests a higher cholinergic tone in mouse than rat, and hence the animal model of choice may have consequences for cholinergic drug testing experiments.

Research highlights▶ Cholinergic innervation patterns and rcholinergic receptor distributions are highly comparable in rat and mouse brain. ▶ Rat brain contains a higher density of cholinergic interneurons than mouse brain. ▶ Mouse brain contains more activated and subsequently internalized muscarinic receptors. ▶ This suggests that cholinergic tone is higher in mouse than rat brain.