artificial theta stimulation impairs encoding of contextual fear memory人工θ刺激损害上下文恐惧记忆的编码.pdf

Artificial Theta Stimulation Impairs Encoding of Contextual Fear Memory 1 1¤ 1 1,2 Arto Lipponen *, Bisrat T. Woldemichael , Kestutis Gurevicius , Heikki Tanila 1 A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland, 2 Department of Neurology, Kuopio University Hospital, Kuopio, Finland Abstract Several experiments have demonstrated an intimate relationship between hippocampal theta rhythm (4–12 Hz) and memory. Lesioning the medial septum or fimbria-fornix, a fiber track connecting the hippocampus and the medial septum, abolishes the theta rhythm and results in a severe impairment in declarative memory. To assess whether there is a causal relationship between hippocampal theta and memory formation we investigated whether restoration of hippocampal theta by electrical stimulation during the encoding phase also restores fimbria-fornix lesion induced memory deficit in rats in the fear conditioning paradigm. Male Wistar rats underwent sham or fimbria-fornix lesion operation. Stimulation electrodes were implanted in the ventral hippocampal commissure and recording electrodes in the septal hippocampus. Artificial theta stimulation of 8 Hz was delivered during 3-min free exploration of the test cage in half of the rats before aversive conditioning with three foot shocks during 2 min. Memory was assessed by total freezing time in the same environment 24 h and 28 h after fear conditioning, and in an intervening test session in a different context. As expected, fimbria-fornix lesion impaired fear memory and dramatically attenuated hippocampal theta power. Artificial theta stimulation produced continuous theta oscillations that were almost similar to endogenous