In the central nervous system, acetylcholinesterase (AChE) is present in a tetrameric form that is anchored to membranes via a proline-rich membrane anchor (PRiMA). Previously it has been found that principal cholinergic neurons in the brain express high concentrations of AChE enzymic activity at their neuronal membranes. The aim of this study was to use immunocytochemical methods to determine the distribution of PRiMA in these neurons in the rat brain. Confocal laser and electron microscopic investigations showed that PRiMA immunoreactivity is associated with the membranes of the somata, dendrites and axons of cholinergic neurons in the basal forebrain, striatum and pedunculopontine nuclei, i.e. the neurons that innervate forebrain and brainstem structures. In these neurones, PRiMA also co-localizes with AChE immunoreactivity at the plasma membrane. PRiMA label was absent from neighboring GABAergic neurons, and from other neurons of the brain known to express high levels of AChE enzymic activity including cranial nerve motor neurons and dopaminergic neurons of the substantia nigra zona compacta. A strong association of AChE with PRiMA at the plasma membrane is therefore a feature specific to principal cholinergic neurons that innervate the central nervous system.
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