CONTEXT

Cholinergic neurons are involved in numerous physiological functions in mammals including motor activity, sleep-wakefulness (vigilance) and cognitive behavior (cognition). The dramatic consequences of the loss of cholinergic
neurons is associated with Alzheimer’s disease, but impairment of the cholinergic system has been also reported in other pathologies, for example in certain forms of epilepsy and in schizophrenia.

One way to investigate the function of cholinergic structures is to analyze the consequences of their impairment. Until recently, the generation of such a loss-of-function phenotype relied on the destruction of cholinergic
neurons by methods which are not specific for these neurons (excitotoxins, electrolytic lesions).

Moreover, constitutive knockout in the mouse of the choline acetyltransferase (ChAT) gene, which is the enzyme of acetylcholine biosynthesis, is further lethal at birth and thus cannot be used to investigate cholinergic function in the adult, while conditional gene knockout requires the slow and costly generation of mice with loxP sites and is
restricted to date to this animal species.