We have determined the volume and location of hippocampal tissue required for normal acquisition of a spatial memory task Ibotenic acid was used to make bilateral symmetric lesions of 20-100% of hippocampal volume. Even a small transverse block (minislab) of the hippocampus (down to 26% of the total) could support spatial learning in a water maze, provided it was at the septal (dorsal) pole of the hippocampus. Lesions Lesions of the hippocampus disrupt learning and retention of spatial maze tasks (1-5). Recordings from pyramidal (6-9) and granule (9, 10) cells demonstrate firing in relation to the spatial position of the animal (place cells), even after relevant spatial cues are removed from the visual field (8,11,12 (>4 h apart). A transfer test, in which the rats swam for 60 s in the absence of the platform, was conducted at the start of days 5 and 7 (before sessions 9 and 13). Time spent swimming in the four quadrants was recorded. Finally, the rats were trained to escape onto a visible platform (three sessions). Curtains were drawn around the pool, and the platform position was varied from trial to trial. Evaluation of Lesions. After i.p. injections of Euthatal (sodium pentobarbital at 200 mg/kg), the rats were perfused intracardially with physiological saline and buffered 4% (vol/ vol) formaldehyde, and the brains were removed and stored in formaldehyde for >1 week. Frozen sections (30 pkm) were cut coronally and stained with thionin. Outlines of the lesions were traced onto 12 coronal line drawings of the hippocampus (19), spaced at 0.5-mm intervals from 1.8 to 7.3 mm posterior to bregma, which allowed determination of the volume of intact hippocampus between each pair of adjacent parallel surfaces. On seven brains with variously sized dorsal or ventral lesions, outlines and estimation of total volume were made by two experimenters (interobserver reliability r = 0.997; differences in volume estimates <3%). Rats with intended complete lesions were excluded if <80% of the hippocampus was damaged.Acetylcholinesterase (AChE). Sections from brains with unilateral dorsal (n = 2) or unilateral ventral (n = 2) hippocampal lesions, medial septal lesions (n = 2), or no lesion (n = 2) were stained for AChE 4 days after the lesion, as described (20).Field Potentials. Rats with ibotenic acid lesions of the ventral or dorsal two-thirds of the hippocampus were anesthetized i.p. with urethane (1.5 g/kg) or tribromoethanol Abbreviation: AChE, acetylcholinesterase. §To whom reprint requests should be sent at the t address. 9697The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.