Inactivating one hippocampus impairs avoidance of a stable room-defined place during dissociation of arena cues from room cues by rotation of the arena

Abstract

Unilateral intrahippocampal injections of tetrodotoxin were used to temporarily inactivate one hippocampus during specific phases of training in an active allothetic place avoidance task. The rat was required to use landmarks in the room to avoid a room-defined sector of a slowly rotating circular arena. The continuous rotation dissociated room cues from arena cues and moved the arena surface through a part of the room in which foot-shock was delivered. The rat had to move away from the shock zone to prevent being transported there by the rotation. Unilateral hippocampal inactivations profoundly impaired acquisition and retrieval of the allothetic place avoidance. Posttraining unilateral hippocampal inactivation also impaired performance in subsequent sessions. This allothetic place avoidance task seems more sensitive to hippocampal disruption than the standard water maze task because the same unilateral hippocampal inactivation does not impair performance of the variable-start, fixed hidden goal task after procedural training. The results suggest that the hippocampus not only encodes allothetic relationships amongst landmarks, it also organizes perceived allothetic stimuli into systems of mutually stable coordinates. The latter function apparently requires greater hippocampal integrity.T he rodent hippocampus is a key neural system for processing information about the current spatial arrangement of stimuli and events (1-4), but it is still unclear what spatial computations the hippocampus actually does. One direction of the current experimental effort in this area is studying what aspects of spatial information the hippocampal network stores (5-12); a second is studying what spatial computations an intact hippocampal system is necessary for (13)(14)(15)(16)(17)(18)(19).It is crucial for this latter approach that there are behavioral paradigms, with clearly defined demands, that subjects must solve by using a limited set of potential solutions. The standard, variable-start, fixed hidden goal place navigation task in the water maze (20) has been invaluable because it allows the optimal solution to be readily distinguished from other less efficient strategies. The optimal strategy is for the rat to learn the allothetic relationships between distant, typically visual stimuli and the position of the escape platform. The absence of stable stimuli on the liquid substrate, like visual and tactile marks and odor cues, and the use of variable start locations make it difficult after standard training for the rat to solve the task optimally by using beacon-guided, praxis, or route-following strategies.Since the early eighties, place learning in the water maze has been used in lesion studies to elucidate the role of the hippocampus in spatial cognition (21,22). Selective bilateral lesions of the dentate gyrus and CA3-CA4 were found to severely impair water maze performance (23). However, in that study, unilateral dentate gyrus lesions, but not CA3-CA4 lesions disturbed water maze performance.One difficulty in interpreting t...

Behavioral Evidence That Segregation and Representation Are Dissociable Hippocampal Functions

“…In line with the hypothesis (Fig. 1), the unilateral TTX injection prevented both learning (Wesierska et al, 2005) and retrieval, and even consolidation (Cimadevilla et al, 2001), of RoomϩArenaϪ avoidance. According to the hypothesis, the segregation demand is too great in RoomϩArenaϪ avoidance to tolerate even mild hippocampal dysfunction (Fig.…”

“…The methods for surgical implantation of guide cannulas and the infusion of TTX have been described previously in detail (Fenton and Bureš, 1993;Fenton et al, 1995;Cimadevilla et al, 2000Cimadevilla et al, , 2001Klement et al, 2005;Wesierska et al, 2005). Rats were anesthetized (50 mg/kg Nembutal; Sigma, St. Louis, MO), and the skull was exposed.…”

“…The place avoidance system (Bio-Signal Group) was adapted from that used in previous studies (Bureš et al, 1997;Fenton et al, 1998;Cimadevilla et al, 2000Cimadevilla et al, , 2001. The arena was a uniform metal disk, 82 cm in diameter, with a 5-cm-high wall.…”

“…Acquisition, retrieval, and consolidation of the place response were abolished when room and arena stimuli were continuously dissociated by rotating the arena (Cimadevilla et al, 2001;Wesierska et al, 2005). According to the distributed memory hypothesis, the minimum number of synapses needed to encode place avoidance memory was not available after the TTX injection.…”

Beyond Memory, Navigation, and Inhibition: Behavioral Evidence for Hippocampus-Dependent Cognitive Coordination in the Rat

“…Unilateral hippocampal dysfunction spared learning in other spatial tasks (Olton et al, 1982;Sutherland et al, 1983;Fenton and Bureš, 1993;Fenton et al, 1995;Moser and Moser, 1998), and we wanted to confirm this for place avoidance as a basis for studying how information is organized between the hippocampi. Injecting TTX into one dorsal hippocampus unexpectedly abolished learning, consolidation, and retrieval of place avoidance on the rotating arena (Cimadevilla et al, 2001).…”