Role of the pedunculopontine tegmental nucleus in sensorimotor gating and reward-related behavior in rats

Rationale The pedunculopontine tegmental nucleus (PPTg) is involved in the execution and regulation of a variety of behaviors. Most investigations used brain lesions that have certain disadvantages, such as functional compensation over time.Objectives In the present study, we investigated by temporary, reversible inhibition of neurons the role of the PPTg in sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR) using variable interstimulus intervals (ISI). In a second set of experiments we examined by the same technique the role of the PPTg in a progressive-ratio instrumental response task.Methods Local infusions of the GABA_A-receptor agonist muscimol (0.05 g and 0.5 g/0.3 l, or vehicle) were applied through indwelling microinfusion cannulae into the PPTg of freely moving rats. ASR and PPI were measured using acoustic stimuli of 100 dB (pulse) and 80 dB (prepulse) using ISIs of 25, 120, 520 and 1,020 ms. Instrumental behavior (lever pressing for casein pellets) was assessed in a Skinner box. Motor activity was measured in an open field.Results Intra-PPTg infusions of muscimol dose-dependently attenuated PPI at ISIs of 120 ms and 520 ms, but not at longer or shorter ISIs. ASR magnitude in pulse-alone trials was not significantly affected. Intra-PPTg infusion of 0.5 g muscimol reduced the break point of instrumental responding (testing sequence where the rats fail to respond according to an increased ratio of reinforcement). No effects on food-preference and open-field activity were found.Conclusions These findings suggest that GABAergic neurotransmission in the PPTg plays an important role for sensorimotor gating at intermediate ISIs and for response selection under demanding schedules of reinforcement.