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


METHODS
Ibotenic acid was microinjected (0.5 microg in 0.05 microL) 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.


METHODS
Sleep research laboratory at Boston University School of Medicine.


METHODS
Adult male Sprague-Dawley rats (N = 27).


METHODS
Chronically implanted for recording polygraphic signs of sleep and bilateral guide tubes for the local microinjections into the P-wave generator.


RESULTS
The ibotenic acid produced a small spherical area (< or = 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.
Mavanji
Vijayakumar
V
Department of Psychiatry, Boston University School of Medicine, Mass 02118, USA.
Ulloor
Jagadish
J
Saha
Subhash
S
Datta
Subimal
S
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D007051:Ibotenic Acid / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D017286:Polysomnography / Q000187:drug effects; D011149:Pons / Q000187:drug effects* / Q000502:physiology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012153:Retention, Psychology / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology
D009498:Neurotoxins; D007051:Ibotenic Acid