Neurotoxic lesions of phasic pontine-wave generator cells impair retention of 2-way active avoidance memory

Abstract

Study Objectives: The aim of this study was to test the hypothesis that the activation of pontine (P)-wave generator is critical for the posttraining rapid eye movement (REM) sleep-dependent memory processing. Design: Ibotenic acid was microinjected (0.5 μg in 0.05 μL) into the functionally identified P-wave generator in order to destroy the cell bodies and thus to study the effects of their destruction upon waking-sleep states, P-waves, and 2-way active avoidance memory. Setting: Sleep research laboratory at Boston University School of Medicine. Participants: Adult male Sprague-Dawley rats (N = 27). Interventions: Chronically implanted for recording polygraphic signs of sleep and bilateral guide tubes for the local microinjections into the P-wave generator. Measurements and Results: The ibotenic acid produced a small spherical area (≤ 0.35 mm in diameter) of nerve cell loss centered on the P-wave generator. Bilateral lesioning of the P-wave generator decreased P-waves during REM sleep by > 95% without significantly changing the amounts of time spent in wake, slow-wave sleep, or REM sleep. In these P-wave generator-lesioned rats, acquisition of avoidance learning and posttraining wake-sleep changes were identical to those of the sham-lesioned rats. However, in the test trials, after 6 hours of undisturbed sleep-wake, P-wave generator-lesioned rats had no retention of avoidance memory. Conclusions: These findings, for the first time, provide direct evidence that P-wave-generating cells are critical for normal REM sleep-dependent memory processing. This evidence supports our hypothesis that the P-wave generator in the brainstem may act as an on switch to provide activating input to forebrain structures for sleep-dependent memory processing.