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MUDr. Jan Bureš, DrSc. |
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Overview of research carrier of Dr. Jan Bures
Dr. Jan Bures, a co-founder of the Laboratory of Neurophysiology of Memory
belongs to the most prominent and well-known brain research scientists in
Czech Republic. His laboratory has been the oldest research units of the
Institute of Physiology ASCR in Prague. The laboratory’s history is reviewed
in more detail by Bureš (2003). It was informally started 50 years ago by
publication of two papers of Dr. Bures on spreading depression (SD) of EEG
activity (Bureš 1954a,b), reporting the possibility to elicit this
remarkable phenomenon in non-anaesthetized rats. This finding stimulated the
rather ambitious project to use local blockade of the depressed brain
regions as a reversible functional ablation procedure (Burešová 1956, Bureš
et al. 1958) and to organize a research group dedicated to this task. Such
unit was officially established in 1958 as the Laboratory of Physiology of
Central Nervous System with Jan Bureš, Olga Burešová, Jiří Křivánek, Eva
Fifková and Tomáš Weiss as the founding members. The method was widely used
in the fifties and sixties to achieve reversible decortication for
investigations concerned with the formation of localized engrams (Bureš and
Burešová 1960a), analysis of their stability, accessibility and migration
(Bureš and Burešová 1960b) and disruption of the memory consolidation
process (Bureš and Burešová 1963).
In the late sixties Dr. Bures pioneered research into the nature of network
connectivity underlying classical conditioning at the level of single
neurons (Bureš and Burešová 1967) by using electrical or iontophoretic
stimulation of the recorded cell as the unconditioned stimulus. In the early
seventies, the laboratory concentrated its efforts on additional behavioral
models, conditioned taste aversion (Burešová and Bureš 1973) and motor
learning (Dolbakyan et al. 1977) and its name was changed to the Laboratory
of Neurophysiology of Memory.
During the last two decades recognition of the importance of animal models
of declarative memory has oriented the laboratory to spatial memory research
(Bureš and Burešová, 1990). Relevant contributions concerned methodological
development in this field (two-level radial maze, aversively motivated
radial maze, on demand platform in the computerized water maze) and the role
of neocortex and hippocampus in the mechanisms of spatial orientation.
For this and other scientific achievements obtained in the past, Dr. Bures
received a membership in th National Academy of Sciences of the USA in ……… (year)
In the last ten years, the research of Dr. Jan Bures has concentrated almost
exclusively on spatial memory of rats and mice while spreading depression,
conditioned taste aversion, and motor learning, in which Dr. Bures achieved
a significant expertise and popularity, have gradually been phased out. The
inaugural PNAS article was an important publication for this period (Bureš
et al. 1997). It formulated the assumption that place cells participate in
navigation behavior and verifying it by experiments making it possible to
record simultaneously place cell activity and place navigation. In the place
avoidance task the rat foraging for food dispersed over a metal arena was
punished by mild foot shock for entering a to be avoided region defined
either in the coordinate system of the room (room frame) or of the arena (arena
frame). When the arena was stable, both systems overlapped and yielded
identical tracks. The rat rapidly learned a passive avoidance of the
punished sector and concentrated its foraging to the safe part of the arena
even when the shock was disconnected.
An interesting situation arises when the arena is made to slowly rotate at 1
rpm (Fenton et al. 1998). A trained rat is now exposed to an ambivalent
state that may sometimes require different responses. It may be far from the
part of arena floor, which was associated with shocks during pre-training in
the stationary situation, but at the same time arena rotation may bring the
rat into the punished room frame location. After 10 to 20 s the above
conditions reverse: the rat is out of the dangerous zone according to its
room frame position but inside it according to its arena frame position.
Strong passive avoidance formed on the stable arena forces the rat to avoid
two places: the room frame defined zone of punishment and the arena frame
defined part of the floor delivering shocks. In the absence of punishment
this “double place avoidance” extinguishes after 2 to 3 sessions, but can be
changed into a permanent response, when the foot shock is applied as soon as
the animal enters either the room frame-defined or the arena frame-defined
sector of its surface. In the first case, the task cannot be solved by
passive avoidance, because rotation of the arena would eventually transport
the rat into the punished sector. Thus the rat has to move against the
rotation of the arena and superimpose this active avoidance on the foraging
in the safe part of the arena. In the second case, when the rat is punished
for entering a specific segment of the arena floor the task can still be
solved by passive avoidance. Finally, it was possible to punish the animal
both for entering the room frame defined and the arena frame defined regions.
This means avoidance of two different places on the rotating arena.
The passive avoidance run without foraging is not very suitable for place
cell recording because it often elicits reduced activity in the parts of the
arena most remote from the punished sector. From this point of view, the
active avoidance on rotating arena is preferable because it forces the
animal to move in circular paths around the center of the arena, but most of
these trajectories are close to the periphery of the arena and are too
narrow to represent standard firing fields.
This disadvantage is absent in the appetitive place preference task, which
was designed by Dr. Jan Bures together with Dr. Jerome Rossier from Lausanne,
Switzerland (Rossier et al. 2000). Rats are trained to find a room frame or
arena frame-defined place on the arena and stay there for 1 s. This triggers
delivery of a food pellet to a random location on the arena. To get the food
the rat has to leave the trigger point and search the arena. After the
pellet has been found, the animal must return to the trigger point to
release another one. The advantage of this arrangement is that the whole
surface of the arena is freely accessible to the foraging rat, which spends
most time (more than 90 %) in random search of the invisible pellet. The
straight goal-directed runs account for only 5 % of the 30-min session. The
place preference task combines the foraging task routinely used for plotting
firing fields of hippocampal place cells with navigation to a hidden
location corresponding to the trigger point activating the feeder. In this
way it is possible to verify the assumption that navigation requires
activity of place cells implementing the cognitive maps that are presumably
indispensable for successful navigation.
First results obtained with this method by the group concentrated around Dr.
Jan Bures (Zinyuk et al. 2000) showed that in rats with long foraging
experience the most firing fields (58 %) recorded on stable arena dissipate
on rotating arena. On the other hand, most firing fields (78 %) recorded in
rats trained in the place preference task remained preserved during rotation
of the arena. The fact that the rats were trained to navigate to a room
frame-defined location on rotating arena was reflected in the ratio of room
frame-defined and arena frame-defined firing fields which was 3/2 in
foragers and 12/3 in navigators. The above results are consonant with the
assumption that navigation to a room frame defined goal needs a support of
room frame- dependent firing fields.
The finding that the arena frame dependent firing fields remain preserved in
darkness suggested that they are supported by idiothesis and tactile or
olfactory intramaze cues. This possibility was examined in experiments
proposed by Dr. Jan Bures and his former student Dr. Ales Stuchlik, in which
parts of arena not contacting the animal were shuffled so that the cues on
arena floor were destabilized and made irrelevant for navigation (Stuchlík
et al. 2001). Active place avoidance in the darkness allowed the animal to
stay outside the prohibited sector of the rotating arena for 10 to 20 min.
This performance mediated by intramaze cue supported idiothesis deteriorated
to 2 min when the surface of the arena was shuffled, probably because the
cumulative errors of path integration could not be corrected by intra-maze
allothesis. Similar result was obtained when the arena was covered by 2 cm
layer of water obliterating the local tactile and olfactory cues so that it
was changed into a wading pool.
Critical role of hippocampus in place navigation has been demonstrated by
lesion and functional ablation studies co-authored by Dr. Jan Bures (e.g.
Fenton and Bureš 1993). Whereas bilateral blockade is required for
disruption of the water maze escape behavior or of the place avoidance task
on stable arena, spatial behavior requiring dissociation of two reference
frames is disrupted already by unilateral blockade elicited by injection of
5 ng of tetrodotoxin (TTX) into one dorsal hippocampus. A simple version of
such behavior is avoidance of a room frame defined of the rotating arena,
which requires the rat to move against the movement of the arena in order to
avoid mild foot shock (Cimadevilla et al. 2001) This active allothetic place
avoidance (AAPA) task is disrupted by hippocampal TTX injection applied
before training (blockade of acquisition), immediately after training (blockade
of memory consolidation) or before retrieval testing (blockade of memory
readout). It seems that AAPA sensitivity to disruption is due to the
necessity to disregard one of the standard reference frames (arena frame)
and pay attention only to the other one (room frame).
In a model of appetitive cooperation designed by Dr. Bures and colleagues
(Svoboda et al. 2003) two rats learn an operant approach-withdrawal task.
When they approach to less than 10 cm to each other, the tracking system
activates the feeder which delivers a pellet onto the arena. The rats
disperse to find the food and to increase their mutual distance to more than
50 cm. When this condition is satisfied, the feeder is loaded with another
pellet and prepared to deliver it when the rats come again together. After
ten training sessions, the rats learned to synchronize their activities and
perform a kind of dance, in which the approach-trigger pellet delivery was
followed by departure in different directions and subsequent pellet search.
The rat, which has found the food, estimates the distance from the other rat
and when it is too short, it tries to increase it. The other rat is either
continuing the search or cooperating by locomotion in opposite direction.
When at least one rat decides that the critical distance has been reached,
it will start the approach run which often coincides with an opposite
movement of the partner rat. Whereas in the predation model only the prey
learns to move in the reference frame formed around the predator, in the
spatial cooperation task both animals can contribute to its successful
solution by assuming proper positions in the reference frame formed by both
animals.
Several papers of group led by Dr. Jan Bures were devoted to place
recognition during passive transport of the animal through familiar
environment. Whereas in the AAPA task the passive transport of the immobile
rat toward the shock sector of the room elicited recognition of the
approaching danger and triggered protective locomotion, in the new
experiments subject’s recognition of a definite position in the environment
indicated availability of reward and was manifested by increased activity in
an operant task. In the first study (Klement and Bureš 2000) a rat in a
Skinner box placed on the periphery of a rotating arena was trained to
observe the experimental room through the transparent centrifugal wall of
the box and to bar press when the long axis of the Skinner box passed
through a 60° sector of the circular trajectory. The rats rapidly learned
the task, started to bar press when the Skinner box approached to –30° from
the reward sector, ceased bar pressing when eating the first pellet and when
passing through the segments of the trajectory opposite the target zone.
Under extinction conditions bar pressing culminated throughout the passage
of the Skinner box across the reward sector, but stopped shortly after the
Skinner box had left the rewarded part of the trajectory.
Results of the above research form the bulk of almost 500 primary articles
and chapters and three monographs (Bureš et al. 1974, 1988, 1998) published
from 1949 to 2003. Throughout its 50-year-long history the laboratory served
as training center hosting more than 100 graduate and postdoctoral students
and visiting scientists from 27 different countries, who coauthored about 50
% of its publication output. The side products of the teaching activities
were several books on neuroscience methods (Bureš et al. 1960, 1976, 1984)
which appeared in repeated English editions and were translated into Russian
and Chinese.
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