Jan Bures

Attention-Like Modulation of Hippocampus Place Cell Discharge

Hippocampus place cell discharge is an important model system for understanding cognition, but evidence is missing that the place code is under the kind of dynamic attentional control characterized in primates as selective activation of one neural representation and suppression of another, competing representation. We investigated the apparent noise (“overdispersion”) in the CA1 place code, hypothesizing that overdispersion results from discharge fluctuations as spatial attention alternates between distal cues and local/self-motion cues. The hypothesis predicts that: (1) preferential use of distal cues will decrease overdispersion; (2) global, attention-like states can be decoded from ensemble discharge such that both the discharge rates and the spatial firing patterns of individual cells will be distinct in the two states; (3) identifying attention-like states improves reconstructions of the rats path from ensemble discharge. These predictions were confirmed, implying that a covert, dynamic attention-like process modulates discharge on a ∼1 s time scale. We conclude the hippocampus place code is a dynamic representation of the spatial information in the immediate focus of attention.

Tetrodotoxin blockade of amygdala overlapping with poisoning impairs acquisition of conditioned taste aversion in rats

The role of several forebrain structures in the association of the short-term gustatory memory (GSTM) of the conditioned stimulus (CS; 0.1% sodium saccharin) with the visceral unconditioned stimulus (US; 0.15 M LiCl, 2% b.wt.) in acquisition of conditioned taste aversion (CTA) was investigated. Experiment 1 examined the effects of bilateral reversible inactivation of amygdala (Amy), hippocampus (Hipp), gustatory cortex (GC), bed nucleus of stria terminalis (BNST), lateral hypothalamic area (LHA), ventral thalamus (VT) or LHA+VT, induced by intracerebral injection of tetrodotoxin (TTX; 10 ng/microliters per site) applied before i.p. injection of LiCl to rats anesthetized by pentobarbital (50 mg/kg) immediately after saccharin drinking. Amy blockade resulted in a complete disruption of learning, while the inactivation of the remaining areas examined produced mild or no impairments. The dose-related effects of TTX injection into Amy were investigated in Experiment 2. Doses of 3 and 1 ng TTX were as effective as the 10 ng dose used in Expt. 1. However, 0.3 ng or saline did not interfere with CTA acquisition. Analysis of the retrograde amnesic effect produced by transient amygdalectomy (Experiment 3), showed that TTX (10 ng) injected immediately or 1.5 h after LiCl application induced a marked learning disruption, whereas no amnesia was elicited at 6 and 24 h post-acquisition intervals. It is suggested that Amy plays an essential role in the associative phase of acquisition, but not in the consolidation of the permanent taste aversion engram.

Passive and active place avoidance as a tool of spatial memory research in rats

A modified model of the arena described by Bures et al. (Bures J, Fenton AA, Kaminsky Y, Zinyuk L. Place cells and place navigation, Proc. Natl. Acad. Sci. USA. 1997a;94:343-350) was applied to the place learning of adult male rats in two different avoidance paradigms. In the passive avoidance task rats exploring a stationary circular arena had to avoid a 60 degrees sector entering of which was punished by mild footshocks. Intramaze as well as extramaze cues could be used for adequate solution of this task. In the active avoidance paradigm rats were trained to avoid a room frame defined sector (e.g. North-East) of a slowly rotating arena the movement of which forced the animals to rely on extramaze cues and to ignore intramaze information. Rats had to find an active solution of the task since otherwise they were passively transported into the room frame defined punished zone. The suitability of these tasks for testing spatial abilities of rats is discussed.

Functional inactivation of dorsal hippocampus impairs active place avoidance in rats

This paper assesses the contribution of hippocampus to the spatial orientation of Long-Evans rats in a new place avoidance task. The animals learn to avoid a mild footshock in a segment of a rotating arena. Since the punished region is defined in the coordinate system of the stationary room the subject is forced to move away from the prohibited segment even if it is immobile. After bilateral injection of tetrodotoxin (5 ng in 1 microl of saline) into the dorsal hippocampus rats were not able to avoid the punished place while a similar injection of saline did not affect performance. The results suggest the task is suitable for assessing the hippocampus-dependent spatial abilities of laboratory rodents.

New spatial cognition tests for mice: Passive place avoidance on stable and active place avoidance on rotating arenas

Dry arenas are a convenient tool for assessing the spatial navigation abilities of rodents. In this paper, mice must avoid a punished sector of a dry arena from which they are expelled by a puff of compressed air. The position of the punished sector is defined relative to the coordinate system of the room. In a stable environment the mice can use both extramaze and intramaze landmarks to orient themselves accurately. However, when the shock area is defined by extramaze landmarks, continuous rotation of the arena at 1 rpm makes it impossible to solve the avoidance task using arena-based cues or idiothesis. The avoidance can only be solved by paying attention to extramaze cues. Our protocol tested spatial abilities on stable and rotating arenas. The acquisition of the task was manifested under both conditions by a significant improvement of performance within the first session (short-term memory component) and at the beginning of the 24-h delayed second session (long-term memory component).

Absence of snapshot memory of the target view interferes with place navigation learning by rats in the water maze.

Contribution of visual and nonvisual mechanisms to spatial behavior of rats in the Morris water maze was studied with a computerized infrared tracking system, which switched off the room lights when the subject entered the inner circular area of the pool with an escape platform. Naive rats trained under light-dark conditions (L-D) found the escape platform more slowly than rats trained in permanent light (L). After group members were swapped, the L-pretrained rats found under L-D conditions the same target faster and eventually approached latencies attained during L navigation. Performance of L-D-trained rats deteriorated in permanent darkness (D) but improved with continued D training. Thus L-D navigation improves gradually by procedural learning (extrapolation of the start-target azimuth into the zero-visibility zone) but remains impaired by lack of immediate visual feedback rather than by absence of the snapshot memory of the target view.

Spatial decisions in rats based on the geometry of computer-generated patterns.

Animals often demonstrate the ability to use the geometric configuration of multiple landmarks for orientation in the environment. We developed a new behavioral task using a computer screen for presentation of visual stimuli allowing the rats to make navigational decisions in real space according to the geometric configuration of external virtual patterns (designed as a possible representation of this space). The rats were placed in a Skinner box with four nosing holes in the transparent front wall through which the computer screen was visible. They were trained in successive phases: first the visual stimulus displayed on the screen directly marked the rewarded nosing hole, then the displayed stimuli were reduced in size or displaced, thus disconnected from the response space. The results suggested that rats were able to use the geometric configuration of stimuli presented on the computer screen for navigational decisions in real space.

Spatial choices of rats based on abstract visual information: Pattern- or configuration-discrimination?

Animals demonstrate their ability to represent a geometric configuration of their environment and to use this information for spatial decisions in their response space in many situations. In presented experiment, we examined the ability of rats to interpret a configuration of abstract visual stimuli to make spatial decisions in a real response space. We tested whether they are able to interpret spatial configuration of abstract stimuli or whether they perceive such visual stimuli simply as geometric patterns associated to particular spatial choices. The rats were tested in a Skinner box with four nosing holes in the transparent front wall through which a computer screen was visible. According to the visual stimuli on the screen, the rats should choose the appropriate nosing hole to obtain a reward. We compared two groups of rats: the first group was exposed to the visual stimuli designed as a representation of the response space: the position of rewarded nosing hole was shown in relation to other nosing holes. The second group was exposed to one of four geometric patterns associated to one of the four nosing holes but without any implicit information about the response space. The results suggested that rats using the stimuli with information about configuration were significantly more successful than rats trained to respond to visual stimuli unrelated to the geometry of the environment.

Dissociating space to understand hippocampal function

Abstract Environments are comprised of multiple spaces, each being a subjective collection of relationships organized into a reference frame of mutually stable features. A rotating arena was used to dissociate the environment into a stationary “room frame” and a rotating “arena frame.” Inactivating one hippocampus with tetrodotoxin (TTX) specifically prevented the learning, the consolidation, and the recall of conditioned place avoidance memories when the relations between (but not within) the room and arena frames were disorganized by rotation. The inactivation did not prevent place avoidance learning when the frame dissociation was prevented by either not rotating the arena, by hiding the stationary room frame cues with darkness, or by hiding the rotating arena frame cues with shallow water. Extracellular unit recordings in anaesthetized rats indicate that the TTX inactivation of one hippocampus silenced it and caused a brief disinhibition in the other hippocampus. Hippocampal activity had returned to preinactivation levels by the time of training. We speculate that the disinhibition marks a physiological reorganization within the hippocampal network that specifically prevented the rat from organizing spatial information from the rotation-disorganized environment. The data indicate that the process of organizing information from disordered stimuli is very sensitive to hippocampal integrity.

Hippocampal Place Cell Activity During Overtly Purposeful Behavior

Since place cell population activity encodes a geometric, map-like representation of the rat’s current environment, it is reasonable to expect that animals use this representation to navigate. This assumption has received substantial correlative support because permanent or temporary dysfunction of the hippocampal formation disturbs allocentric navigational behavior (Jarrard, 1980; Morris et al., 1982; Sutherland et al., 1982). Unfortunately, the correlation between the existence of hippocampal place cells and the dependence on an intact hippocampus for optimal allothetic spatial behavior neither establishes nor elucidates a causal relationship between place cell firing and navigation behavior.Andre A. Fenton,2, Jan Bures!, Jose Manuel Cimadevilla, Andrey V. Olypher4, Malgorzata Wesierska, and Larissa Zinyuk IInstitute ofPhysiology, Academy of Sciences of the Czech Republic, 2Dept. Physiology & Pharmacology SUNY, Downstate Medical Center, 3Dept. Experimental Psychology & Psychobiology, University ofAlmeria, Spain,4Dept. Mechanics and Mathematics, Rostov State University, Russia, ~encki Institute ofExperimental Biology, Warsaw, Poland, 6Centre Europeen des Sciences du Gout -eNRS, France.