Role of the Cholinergic Pedunculopontine Tegmental Nucleus in Long-term Habituation

The cholinergic system is implicated in long-term habituation, which is the decrease in response across test sessions following repeated exposure to a stimulus. A potential structure involved is the pedunculopontine tegmental nucleus (PPT). We hypothesized that cholinergic PPT neurons mediate long-term habituation of the acoustic startle response (ASR), but not exploratory behaviour in an open field. Transgenic rats expressing Cre recombinase in cholinergic cells were microinjected with a Cre-dependent virus encoding the inhibitory hM4Di DREADD or respective control construct into the PPT. After the successful behavioural validation of the transgenic ratline, long-term habituation was tested over five days following systemic delivery of the hM4Di DREADD activator or vehicle. There was no effect of inhibiting cholinergic PPT neurons on long-term habituation in either paradigm. This suggests the PPT is not the source of cholinergic modulation of long-term habituation in these paradigms and further investigation into underlying mechanisms is required