Lateralized Fascia Dentata Lesion and Blockade of One Hippocampus: Effect on Spatial Memory in Rats Boldizsa ´r Cze ´h, 1,2 La ´szlo ´ Seress, 3 Lynn Nadel, 4 and Jan Bures 2 * 1 Department of Physiology, University Medical School Pe ´cs, Szigeti-u., Pe ´cs, Hungary 2 Institute of Physiology, Academy of Sciences of Czech Republic, Videnska, Prague, Czech Republic 3 Central Electron Microscopic Laboratory, University Medical School Pe ´cs, Szigeti-u., Pe ´cs, Hungary 4 Department of Psychology, University of Arizona, Tucson, Arizona, USA ABSTRACT: U nilateral blockade of the dorsal hippocampus by tetrodo- toxin makesit possible to form lateralized spatial memories, which rapidly transfer to the naive hippocampus when training continues with intact brain. Unilateral X-ray irradiation of newborn rats causes irreversible destruction of granule cells in the ipsilateral fascia dentata (FD). Possible compensation of poor learning in the lesioned hemisphere by commissural transfer of memories from the intact hippocampus was examined in seven ratswith unilateral FD lesion, which were first trained in the Morriswater maze to asymptotic performance (mean escape latency 6  1 s). Subsequent testing during functional ablation either of the intact or of the lesioned hippocampus by tetrodotoxin revealed escape latencies 35  8s or 8  1 s, respectively. Probe trial tests during inactivation of the intact and lesioned hippocampusshowed target quadrant preference of 32  2% or 54 3% , respectively. The resultsindicate: (a) that one intact hippocam- pus alone can support the water maze task, (b) that no, or only a very weak, memory trace is available in the lesioned hippocampus. It is concluded that the above results are due to the inability of the FD lesioned hippocampus to process the information received from the ipsilateral entorhinal cortex. Hippocampus1998;8:647–650.  1998 Wiley-Liss, Inc. KEY W O RD S: neonatal X-irradiation; tetrodotoxin; water maze; inter- hemispheric transfer INTRODUCTION Interhemispheric transfer (IHT ) of lateralized engrams demonstrates that what is learned with one side of the brain can be not only retrieved and used by the other side, but even copied into the naive side. Unilateral functional blockade by tetrodotoxin (TT X) or lidocaine injection into fimbria-fornix and dorsal hippocampus (Fenton and Bures, 1993, 1994) makes it possible to form lateralized spatial memories which can be rapidly transferred from the trained to the naive hippocampus after the latter recovers (Fenton et al., 1995). It was suggested that the transfer is mediated by interhippocampal commissural pathways activated when the task is performed with intact brain. Focal X-ray irradiation of neonatal rats makes it possible to induce selective and massive reduction in the number of granule cells of the fascia dentata (Bayer and Altman, 1975). A single high dose of bilateral X-ray irradiation applied on the first postnatal day elicits a large loss of granule cells manifested by severe spatial navigation deficit in adult rats tested in the Morris water maze (Czurko et al., 1997). Lateralized irradiation destroying the fascia dentata (FD) only in one hemisphere makes it possible to compare place navigation during unilateral functional ablation of the irradiated or of the intact hippocampus. We asked whether the absence of the spatial learning deficit in the unilaterally irradiated rats can be due not only to the normal function of the intact hippocampus but also to spatial learning supported in the irradiated hippocampus by the commissurally mediated input from the intact hemisphere. METHODS AND PROCEDURE For detailed methodological description of the irradia- tion procedure, testing apparatus, behavioral tests, histol- ogy, and data analysis see Czurko et al. (1997). T he T T X functional lesioning technique was described by Fenton and Bures (1993). Briefly, seven Long-Evans, newborn Grant sponsor: Hungarian Science Foundation; Grant number: T017776; Grant sponsor: FKFP; Grant number: 0951/1997; Grant sponsor: James McDonnell Foundation; Grant number: 95–14; Grant sponsor: Czech Republic; Grant number: 309/97/0555. *Correspondence to: Dr. Jan Bures, Institute of Physiology, Academy of Sciences of Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic. E-mail: bures@biomed.cas.cz Accepted for publication 8 August 1998 HIPPOCAMPUS 8:647–650 (1998)  1998 WILEY-LISS, INC.