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Hana Mala - One of the best experts on this subject based on the ideXlab platform.

  • Erythropoietin improves spatial delayed alternation in a T-maze in Fimbria-Fornix transected rats
    Behavioural brain research, 2007
    Co-Authors: Jesper Mogensen, Christina Jensen, Siff Camilla Kingod, Asbjørn Hansen, Jan Abildtrup Rode Larsen, Hana Mala
    Abstract:

    Systemically administered human recombinant erythropoietin (EPO) may have the potential to reduce the cognitive and behavioural symptoms of a mechanical brain injury. In a series of studies we address this possibility. We have previously found that EPO given to Fimbria-Fornix transected rats at the moment of injury is able substantially to improve the posttraumatic acquisition of allocentric place learning tasks administered in a water maze as well as in an 8-arm radial maze. It is, however, essential to evaluate this clinically important ability of EPO within other cognitive domains, as well. Consequently, we presently studied the effects of similarly administered EPO in Fimbria-Fornix transected and control operated rats, respectively--evaluating the posttraumatic behavioural/cognitive abilities in a spatial delayed alternation task performed in a T-maze. Administration of EPO to the hippocampally injured rats was associated with a substantial reduction of the lesion-associated behavioural impairment--while such an impairment was clearly seen in the saline injected Fimbria-Fornix transected group. In contrast, EPO had no detectable effect on the task acquisition of non-lesioned animals. The results of the present study confirm our previous demonstrations that EPO is able to reduce or eliminate the behavioural/cognitive consequences of mechanical injury to the hippocampus--and emphasize that this ability is present across a broader spectrum of cognitive domains.

  • prefrontal cortex and hippocampus in posttraumatic functional recovery spatial delayed alternation by rats subjected to transection of the fimbria fornix and or ablation of the prefrontal cortex
    Brain Research Bulletin, 2007
    Co-Authors: Jesper Mogensen, Jens Hjortkjaer, Kenneth L Ibervang, Kristin Stedal, Hana Mala
    Abstract:

    Abstract Lesions of the prefrontal cortex and the hippocampus often lead to impairment of the same behavioural tasks (e.g., allocentric as well as egocentric spatial orientation and spatial delayed alternation). In case of allocentric and egocentric spatial orientation we have previously found that the two structures mutually contribute to the posttraumatic functional recovery of such tasks. We therefore presently tested the hypothesis that this would even be true in case of spatial delayed alternation. The acquisition of a spatial delayed alternation task in a T-maze was studied in four groups of rats: animals in which the fimbria–fornix had been transected bilaterally, rats who had received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham operated control group. All three lesion groups demonstrated an impaired task acquisition. The group given prefrontal cortical lesions in isolation underwent a complete functional recovery. Both of the fimbria–fornix transected groups were significantly impaired even when compared to the group given prefrontal cortical ablations in isolation. The two fimbria–fornix lesioned groups did, however, exhibit levels of functional recovery. The group in which both structures had been lesioned demonstrated a task acquisition, which was significantly inferior to that of the group given fimbria–fornix transections in isolation. After completion of the task acquisition period, all animals were subjected to two behavioural challenges including a session on which the duration of the inter-trial delay was doubled. This expansion of the inter-trial delay rather selectively impaired the task performance of the group given fimbria–fornix transections in isolation. Consequently, both during the acquisition period and in one of the challenges a differentiation of functional recovery was seen between the combined lesioned group and the group given fimbria–fornix lesions only. This indicates that even in case of a spatial delayed alternation task the prefrontal cortex normally contributes significantly to mediation of posttraumatic functional recovery after isolated lesions of the fimbria–fornix. The results are discussed in the context of models of posttraumatic functional recovery.

  • erythropoietin improves place learning in fimbria fornix transected rats and modifies the search pattern of normal rats
    Pharmacology Biochemistry and Behavior, 2004
    Co-Authors: Jesper Mogensen, Kamilla W Miskowiak, Thomas Alrik Sorensen, Christopher Trier Lind, Niels Vidiendal Olsen, Jacob Bertram Springborg, Hana Mala
    Abstract:

    Abstract The acquisition of a water-maze-based allocentric place learning task was studied in four groups of rats: two groups subjected to bilateral transections of the fimbria–fornix and two groups undergoing a sham control operation. At the moment of surgery all animals were given one systemic (intraperitoneal) injection of either human recombinant erythropoietin (EPO) (at a dosage of 5000 IU/kg body weight), given to one of the fimbria–fornix-transected groups and one of the sham-operated groups, or vehicle (saline), given to the two remaining groups. The 25-day task acquisition period (one session/day) began 6 or 7 days after the day of surgery. The fimbria–fornix-transected and saline-injected group exhibited a pronounced and long-lasting impairment of task acquisition. In contrast, the fimbria–fornix-transected and EPO-treated group demonstrated a less pronounced and more transient lesion-associated impairment. The two sham-operated groups did not differ with respect to the proficiency of task acquisition. But administration of EPO to intact animals caused a significant modification of swim patterns—apparently reflecting a somewhat modified strategy of task solution. It is concluded that systemic administration of EPO significantly improves the posttraumatic functional recovery of the presently studied place learning task after transections of the fimbria–fornix. Additionally, administration of EPO influences the strategy, although not quality, of task solution in normal (sham-operated) rats.

Jean-christophe Cassel - One of the best experts on this subject based on the ideXlab platform.

  • a comparison of the effects of fimbria fornix hippocampal or entorhinal cortex lesions on spatial reference and working memory in rats short versus long postsurgical recovery period
    Neurobiology of Learning and Memory, 2002
    Co-Authors: Rodrigue Galani, Etienne Coutureau, Leonard E Jarrard, Stephanie Obis, Jean-christophe Cassel
    Abstract:

    Using a radial maze task and different postoperative recovery periods, this experiment assessed and compared the reference and working memory performances of adult Long-Evans male rats subjected to entorhinal cortex, Fimbria-Fornix, and hippocampus lesions. Sham-operated rats were used as controls. In order to see whether the duration of the postsurgical recovery period would influence acquisition of the complex radial maze task, training began 1 month following surgery (Delay 1) for half the rats in each group, while for the other half training was started 6.5 months following surgery (Delay 2). The results indicated that at both recovery periods the entorhinal cortex lesions failed to affect either working or reference memory in the spatial task. Conversely, both Fimbria-Fornix and hippocampus lesions impaired both reference and working memory. While the reference memory deficit was generally similar in both Fimbria-Fornix and hippocampal lesion groups, analysis of the results for working memory indicated that at the longer delay rats with Fimbria-Fornix lesions were still impaired but in animals that had the hippocampus removed, working memory did not differ from that of controls. These results suggest that there was some recovery in those rats with hippocampal lesions (e.g., on the working memory task) but both hippocampal and Fimbria-Fornix animals were still impaired compared to controls when training was delayed 6.5 months following the operations.

  • selective lesions of the entorhinal cortex the hippocampus or the fimbria fornix in rats a comparison of effects on spontaneous and amphetamine induced locomotion
    Experimental Brain Research, 2000
    Co-Authors: Etienne Coutureau, Rodrigue Galani, Leonard E Jarrard, Jean-christophe Cassel
    Abstract:

    Using adult Long-Evans male rats, this experiment compared spontaneous (assessed 15 days and 4.5 months after surgery) and amphetamine-induced (assessed from 4.5 months after surgery onwards; 1 mg/kg, i.p., ten injections, 48 h apart) locomotor activity following N-methyl-d-aspartate lesions of the entorhinal cortex, electrolytic lesions of the Fimbria-Fornix, or ibotenate lesions of the hippocampus. Sham-operated rats were used as controls. Hippocampal and Fimbria-Fornix lesions, but not entorhinal-cortex lesions induced diurnal and nocturnal hyperactivity, which was attenuated over time, but only in rats with Fimbria-Fornix lesions. Amphetamine-induced hyperlocomotion was assessed in a familiar environment. Lesions of the entorhinal cortex potentiated the locomotor effects of amphetamine, but not lesions of the hippocampus or interruption of the axons in the Fimbria-Fornix pathway. Sensitization appeared to be decreased by Fimbria-Fornix lesions and to be prevented by hippocampal lesions. Rats with entorhinal-cortex lesions behaved as if they had already been sensitized by the lesion. These results clearly show that lesions of the Fimbria-Fornix, the hippocampus, and of the entorhinal cortex have different effects on spontaneous and amphetamine-induced hyperactivity, as they also have on learning and memory tasks.

  • A comparison of the effects of two Fimbria-Fornix lesion techniques on beam-walking performance in the rat : aspiration versus electrolysis
    Behavioural Brain Research, 1996
    Co-Authors: Elee Hofferer, Jean-christophe Cassel
    Abstract:

    This experiment was aimed at comparing the sensorimotor correlates of Fimbria-Fornix lesions made with either a classical aspiration technique that also removes part of the overlying cortical structures, or an electrolytic one that does not encroach upon these cortical structures. About 4 months after lesion surgery, Long-Evans female rats which had sustained an aspiration or an electrolytic Fimbria-Fornix lesion at the age of 90 days were tested to measure their beam-walking performance as an index for their sensorimotor capabilities. We found that after an aspiration lesion, the rats presented sensorimotor deficits which did not occur after an electrolytic lesion. After having found that electrolytic lesions of the fimbria and the fornix produced neurochemical deficits (in the dorsal hippocampus) and cognitive alterations close to those resulting from aspiration lesions, it is concluded from the present experiment that the electrolytic lesion technique is an interesting alternative to an aspiration technique, essentially because the former does not induce the sensorimotor deficits due to the partial damage that an aspiration technique produces in the medial parietal cortex. As the electrolytic lesion technique may minimize the risk of introducing a sensorimotor bias in the accuracy of cognitive evaluations, the present result might be of interest to neuroscientist using a Fimbria-Fornix lesion paradigm in order to investigate the efficacy of drugs, grafts or other treatments on the recovery from cognitive deficits.

  • "Short-stops" in rats with Fimbria-Fornix lesions: evidence for change in the mobility gradient.
    Hippocampus, 1994
    Co-Authors: Ian Q. Whishaw, Jean-christophe Cassel, Monique Majchrzak, Suzanne Cassel, Bruno Will
    Abstract:

    Rats with damage to the hippocampal formation and allied structures are hyperactive in many test situations but the cause of this hyperactivity is not known. Here the activity of control rats and rats with Fimbria-Fornix lesions is documented in tests of overnight activity. Details of activity are then characterized from video recordings of behavior in an open field. Rats with Fimbria-Fornix lesions make significantly more stops of shorter duration and thus more individual trips than control rats but they do not differ in the distance traveled on individual trips or in travel speed. It is suggested that the main difference between Fimbria-Fornix rats and control rats is that when Fimbria-Fornix rats stop they remain “still” for shorter durations than do control rats. This finding is discussed in relation to a theory of locomotor/exploratory behavior, and in relation to its implications with respect to the performance of Fimbria-Fornix rats in studies of learning and memory. © 1994 Wiley-Liss, Inc.

  • Morphological and behavioural effects of granule cell degeneration induced by intrahippocampal fluid injections in intact and Fimbria-Fornix lesioned rats.
    Behavioural brain research, 1994
    Co-Authors: Elee Hofferer, Jean-christophe Cassel, Christian Kelche, P. Millemann, Bruno Will
    Abstract:

    Abstract This study was aimed at determining whether granule cell degeneration induced by intragyral injections of a neutral fluid (0.9% NaCl with 0.6% glucose, pH 7.0, 2 sites per hippocampus, 2 μl/site, 1 μl/min) produced behavioural deficits in rats which, 2 weeks prior to the injections, had received either Fimbria-Fornix lesions or sham-operations. In both sham-operated and lesioned rats, we found such injections to induce a comparable, topographically-limited loss of granule cells in the dorsal leaf of the dentate gyrus and, in the close vicinity of the degeneration area, a severe shrinkage of the molecular layer with concomitant morphological reorganizations (e.g. acetylcholinesterase reaction products were distributed uniformly throughout the molecular layers of sham-operated rats). While the Fimbria-Fornix lesions produced classically reported behavioural deficits (hyperactivity in both a familiar and an unfamiliar environment, reduced T-maze alternation rates and impaired radial-maze performance), we could not detect adversive effects of the granule cell degeneration on either of these variables in sham-operated and lesioned rats. Our data suggest that limited granule cell degeneration induced by intragyral fluid injections has no effect on locomotor activity, spontaneous alternation and spatial learning. Therefore, we may also infer that the granule cell damage observed after an intragyral implantation of a fetal neural cell suspension does probably not account for the behavioural deficits which, in some experiments, have been found in Fimbria-Fornix lesioned rats bearing intragyral cell suspension grafts.

Ian Q. Whishaw - One of the best experts on this subject based on the ideXlab platform.

  • fimbria fornix lesions disrupt the dead reckoning homing component of exploratory behavior in mice
    Learning & Memory, 2002
    Co-Authors: Joanna H Gorny, Douglas G Wallace, Bogdan Gorny, Ian Q. Whishaw
    Abstract:

    Exploration is the primary way in which rodents gather information about their spatial surroundings. Thus, spatial theories propose that damage to the hippocampus, a structure thought to play a fundamental role in spatial behavior, should disrupt exploration. Exploration in rats is organized. The animals create home bases that are central to exploratory excursions and returns, and hippocampal formation damage alters the organization of exploration by disrupting returns. Mice do not appear to readily establish home bases in novel environments, thus, for this species, it is more difficult to establish the contribution of the hippocampus to exploration. The purpose of the present study was threefold: develop a task in which mice center their exploration from a home base, determine whether the exploratory behavior is organized, and evaluate the role of Fimbria-Fornix lesions on exploration. Mice were given a novel exploratory task in which their nesting material was placed on a large circular table. Video records of control and Fimbria-Fornix mice were made in both light and dark (infrared light) conditions. Exploration patterns (outward trips, stops, and homeward trips) were reconstructed from the video records. Control mice centered their activity on their bedding, from which they made circuitous outward trips marked by many stops, and periodic direct returns. The bedding-centered behavior and outward trips of the Fimbria-Fornix mice were similar to those of the control mice, but significantly fewer direct return trips occurred. The direct homeward trips observed under light and dark conditions were consistent with a dead-reckoning strategy, in which an animal computes its present position and homeward trajectory from self-movement cues generated on the outward trip. Because the Fimbria-Fornix lesions disrupted the homeward component of exploratory trips, we conclude that the Fimbria-Fornix may contribute to dead reckoning in mice. The results also show that the home-bedding methodology facilitates the establishment of a home base by mice, thus providing a useful methodology for studies with mice.

  • Impaired dodging in food-conflict following Fimbria-Fornix transection in rats: a novel hippocampal formation deficit.
    Brain research bulletin, 2002
    Co-Authors: Scott D. Oddie, Ian Q. Whishaw, Ian J. Kirk, Boguslaw P. Gorny, Brian H. Bland
    Abstract:

    It is well known that damage to the hippocampal formation (Ammon's horn, dentate gyrus, Fimbria-Fornix, and other pathways) produces impairments in spatial navigation and in certain forms of learning. Lesions within these structures have also been reported to produce some motor impairments, but the nature of these impairments is less understood. The present study examined the effects of Fimbria-Fornix lesions on food wrenching and dodging, social interactions that occur when one rat attempts to steal food from a conspecific, who in turn attempts to protect the food by an evasive movement. Lesion effectiveness was confirmed histologically and electrophysiologically, by the loss of hippocampal rhythmical slow-wave activity (RSA or theta), and by changes in open field behavior (increased open field behavior, less thigmotaxis and more defecation). Analysis of the social interaction indicated when an eating control rat was approached by a conspecific that was attempting to steal its food, it prevented the theft by dodging, a rapid lateral maneuver involving forequarter turning and stepping with the rear limbs. Rats with Fimbria-Fornix lesions were significantly impaired in dodging and so were more likely to lose their food to the robber. This novel deficit in motor behavior is discussed in relation to contemporary theories of hippocampal function and it is suggested that the deficit may be caused by an inability of the Fimbria-Fornix damaged animals to disengage attention from eating in order to initiate an evasive movement to protect food. The finding of this novel deficit underscores the importance of considering both loss as well as release phenomena in the analysis of hippocampal formation function.

  • dead reckoning path integration requires the hippocampal formation evidence from spontaneous exploration and spatial learning tasks in light allothetic and dark idiothetic tests
    Behavioural Brain Research, 2001
    Co-Authors: Ian Q. Whishaw, Dustin J Hines, Douglas G Wallace
    Abstract:

    Animals navigate using cues generated by their own movements (self-movement cues or idiothetic cues), as well as the cues they encounter in their environment (distal cues or allothetic cues). Animals use these cues to navigate in two different ways. When dead reckoning (deduced reckoning or path integration), they integrate self-movement cues over time to locate a present position or to return to a starting location. When piloting, they use allothetic cues as beacons, or they use the relational properties of allothetic cues to locate places in space. The neural structures involved in cue use and navigational strategies are still poorly understood, although considerable attention is directed toward the contributions of the hippocampal formation (hippocampus and associated pathways and structures, including the Fimbria-Fornix and the retrosplenial cortex). In the present study, using tests in allothetic and idiothetic paradigms, we present four lines of evidence to support the hypothesis that the hippocampal formation plays a central role in dead reckoning. (1) Control but not Fimbria-Fornix lesion rats can return to a novel refuge location in both light and dark (infrared) food carrying tasks. (2). Control but not Fimbria-Fornix lesion rats make periodic direct high velocity returns to a starting location in both light and dark exploratory tests. Control but not Fimbria-Fornix rats trained in the light to carry food from a fixed location to a refuge are able to maintain accurate outward and homebound trajectories when tested in the dark. (3). Control but not Fimbria-Fornix rats are able to correct an outward trajectory to a food source when the food source is moved when allothetic cues are present. These, tests of spontaneous exploration and foraging suggest a role for the hippocampal formation in dead reckoning. © 2001 Elsevier Science B.V. All rights reserved.

  • Rats with Fimbria-Fornix lesions can acquire and retain a visual-tactile transwitching (configural) task.
    Behavioral Neuroscience, 1995
    Co-Authors: Ian Q. Whishaw, Jo-anne Tomie
    Abstract:

    : The idea that the hippocampus is essential for acquisition and retention of a transwitching (configural) problem is evaluated with a visual-tactile task. The task requires the rats to pull up a string of one of two sizes for food, as signalled by room lighting conditions. Rats received cathodal Fimbria-Fornix lesions either prior to or after learning the task. Rats with Fimbria-Fornix lesions were unimpaired in acquisition or retention. The results do not support the position that the hippocampal formation is essential for the acquisition and retention of a transwitching configural problem. The result is discussed in relation to the configural theory of hippocampal function.

  • similarities vs differences in place learning and circadian activity in rats after fimbria fornix section or ibotenate removal of hippocampal cells
    Hippocampus, 1995
    Co-Authors: Leonard E Jarrard, Ian Q. Whishaw
    Abstract:

    Damage to either the Fimbria-Fornix or to the hippocampus can produce a deficit in spatial behavior and change in locomotor activity but the extent to which the two kinds of damage are comparable is not known. Here we contrasted the effects of cathodal sections of the Fimbria-Fornix with ibotenic acid lesions of the cells of the hippocampus (Ammon's horn and the dentate gyrus) on place learning in a swimming pool and on circadian activity. Rats in both ablation groups were impaired relative to control rats in learning a single place response but they did acquire the response as measured by swim latencies, errors, and by enhanced searching on probe trials. They were also more active than the control group on the test of activity. Nevertheless, the Fimbria-Fornix group was initially more impaired on learning and was more active than the hippocampal group. Analysis of the strategies used in learning indicated that the lesion groups were very similar to each other but different from the control group especially in that at asymptotic performance, rats in both lesion groups made rather tight loops as they swam toward the platform. This strategy likely contributed to the greater proportion of time they spent swimming in the correct quadrant on the subsequent probe trial. These findings confirm that rats with Fimbria-Fornix or hippocampal damage display impairments in place learning and are hyperactive but also show that there are lesion differences. The results are discussed with respect to the relative effectiveness of the lesions and the possibility that fibers in the Fimbria-Fornix may mediate some functions that are not attributable to the hippocampus. © 1995 Wiley-Liss, Inc.

Jesper Mogensen - One of the best experts on this subject based on the ideXlab platform.

  • PLACE LEARNING BY Fimbria-Fornix TRANSECTED RATS IN A MODIFIED WATER MAZE
    International Journal of Neuroscience, 2009
    Co-Authors: Gitta Wörtwein, Lise Holm Saerup, Davy Charlottenfeld-starpov, Jesper Mogensen
    Abstract:

    The acquisition of a place learning task in a water maze modified from the “standard” setup by restriction of distal cues was tested in two groups of rats: (1) animals subjected to bilateral transection of the Fimbria-Fornix—a manipulation that renders the hippocampus dysfunctional—and (2) a sham operated control group. The Fimbria-Fornix transected animals acquired the task as quickly and to the same level of proficiency as the control group. Upon reaching criterion level performance all animals were tested on “rotation” sessions on which the distal cues were displaced. The outcome of such “rotations” demonstrated that both groups relied upon the distal cues for navigational purposes. Finally, the performance of all animals was “challenged” on two sessions by administration of d-amphetamine and scopolamine, respectively. The outcome of the pharmacological challenges demonstrated that the normal proficiency of place learning by the Fimbria-Fornix transected rats had been accomplished due to compensatory p...

  • Erythropoietin improves spatial delayed alternation in a T-maze in Fimbria-Fornix transected rats
    Behavioural brain research, 2007
    Co-Authors: Jesper Mogensen, Christina Jensen, Siff Camilla Kingod, Asbjørn Hansen, Jan Abildtrup Rode Larsen, Hana Mala
    Abstract:

    Systemically administered human recombinant erythropoietin (EPO) may have the potential to reduce the cognitive and behavioural symptoms of a mechanical brain injury. In a series of studies we address this possibility. We have previously found that EPO given to Fimbria-Fornix transected rats at the moment of injury is able substantially to improve the posttraumatic acquisition of allocentric place learning tasks administered in a water maze as well as in an 8-arm radial maze. It is, however, essential to evaluate this clinically important ability of EPO within other cognitive domains, as well. Consequently, we presently studied the effects of similarly administered EPO in Fimbria-Fornix transected and control operated rats, respectively--evaluating the posttraumatic behavioural/cognitive abilities in a spatial delayed alternation task performed in a T-maze. Administration of EPO to the hippocampally injured rats was associated with a substantial reduction of the lesion-associated behavioural impairment--while such an impairment was clearly seen in the saline injected Fimbria-Fornix transected group. In contrast, EPO had no detectable effect on the task acquisition of non-lesioned animals. The results of the present study confirm our previous demonstrations that EPO is able to reduce or eliminate the behavioural/cognitive consequences of mechanical injury to the hippocampus--and emphasize that this ability is present across a broader spectrum of cognitive domains.

  • prefrontal cortex and hippocampus in posttraumatic functional recovery spatial delayed alternation by rats subjected to transection of the fimbria fornix and or ablation of the prefrontal cortex
    Brain Research Bulletin, 2007
    Co-Authors: Jesper Mogensen, Jens Hjortkjaer, Kenneth L Ibervang, Kristin Stedal, Hana Mala
    Abstract:

    Abstract Lesions of the prefrontal cortex and the hippocampus often lead to impairment of the same behavioural tasks (e.g., allocentric as well as egocentric spatial orientation and spatial delayed alternation). In case of allocentric and egocentric spatial orientation we have previously found that the two structures mutually contribute to the posttraumatic functional recovery of such tasks. We therefore presently tested the hypothesis that this would even be true in case of spatial delayed alternation. The acquisition of a spatial delayed alternation task in a T-maze was studied in four groups of rats: animals in which the fimbria–fornix had been transected bilaterally, rats who had received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham operated control group. All three lesion groups demonstrated an impaired task acquisition. The group given prefrontal cortical lesions in isolation underwent a complete functional recovery. Both of the fimbria–fornix transected groups were significantly impaired even when compared to the group given prefrontal cortical ablations in isolation. The two fimbria–fornix lesioned groups did, however, exhibit levels of functional recovery. The group in which both structures had been lesioned demonstrated a task acquisition, which was significantly inferior to that of the group given fimbria–fornix transections in isolation. After completion of the task acquisition period, all animals were subjected to two behavioural challenges including a session on which the duration of the inter-trial delay was doubled. This expansion of the inter-trial delay rather selectively impaired the task performance of the group given fimbria–fornix transections in isolation. Consequently, both during the acquisition period and in one of the challenges a differentiation of functional recovery was seen between the combined lesioned group and the group given fimbria–fornix lesions only. This indicates that even in case of a spatial delayed alternation task the prefrontal cortex normally contributes significantly to mediation of posttraumatic functional recovery after isolated lesions of the fimbria–fornix. The results are discussed in the context of models of posttraumatic functional recovery.

  • Place learning and object recognition by rats subjected to transection of the Fimbria-Fornix and/or ablation of the prefrontal cortex.
    Brain Research Bulletin, 2004
    Co-Authors: Jesper Mogensen, Klara Tølbøll Lauritsen, Soheyla Elvertorp, Andreas Hasman, Anette Moustgaard, Gitta Wörtwein
    Abstract:

    The acquisition of a water maze-based allocentric place learning task and an exploration based object recognition task were studied in four groups of rats: animals in which the Fimbria-Fornix had been transected, rats who had received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham operated control group. None of the groups showed impairments of object recognition. Ablations of the prefrontal cortex caused a mild impairment in the acquisition of the place learning task. The two Fimbria-Fornix transected groups exhibited a severe impairment during the acquisition of this task. All groups reached criterion level task performance eventually. All groups were subjected to a number of behavioural and pharmacological challenges in order to elucidate the neural and cognitive mechanisms of this behavioural recovery. During a no-platform session both the Fimbria-Fornix transected group and the prefrontally ablated group demonstrated a normal preference for the former platform position. The combined lesion group, however, failed to show a similar preference for this position. The outcome of the pharmacological challenges demonstrated that while the task performance of all four groups relied equally on catecholaminergic mediation, only the task solution of the Fimbria-Fornix transected group was significantly impaired by disturbance of the catecholaminergic systems. The data indicated a high likelihood that prefrontal cortical mechanisms contribute to the recovery of allocentric place learning after Fimbria-Fornix transections.

  • erythropoietin improves place learning in fimbria fornix transected rats and modifies the search pattern of normal rats
    Pharmacology Biochemistry and Behavior, 2004
    Co-Authors: Jesper Mogensen, Kamilla W Miskowiak, Thomas Alrik Sorensen, Christopher Trier Lind, Niels Vidiendal Olsen, Jacob Bertram Springborg, Hana Mala
    Abstract:

    Abstract The acquisition of a water-maze-based allocentric place learning task was studied in four groups of rats: two groups subjected to bilateral transections of the fimbria–fornix and two groups undergoing a sham control operation. At the moment of surgery all animals were given one systemic (intraperitoneal) injection of either human recombinant erythropoietin (EPO) (at a dosage of 5000 IU/kg body weight), given to one of the fimbria–fornix-transected groups and one of the sham-operated groups, or vehicle (saline), given to the two remaining groups. The 25-day task acquisition period (one session/day) began 6 or 7 days after the day of surgery. The fimbria–fornix-transected and saline-injected group exhibited a pronounced and long-lasting impairment of task acquisition. In contrast, the fimbria–fornix-transected and EPO-treated group demonstrated a less pronounced and more transient lesion-associated impairment. The two sham-operated groups did not differ with respect to the proficiency of task acquisition. But administration of EPO to intact animals caused a significant modification of swim patterns—apparently reflecting a somewhat modified strategy of task solution. It is concluded that systemic administration of EPO significantly improves the posttraumatic functional recovery of the presently studied place learning task after transections of the fimbria–fornix. Additionally, administration of EPO influences the strategy, although not quality, of task solution in normal (sham-operated) rats.

Michael Frotscher - One of the best experts on this subject based on the ideXlab platform.

  • Transient Up‐regulation of Ciliary Neurotrophic Factor Receptor‐α mRNA in Axotomized Rat Septa1 Neurons
    European Journal of Neuroscience, 1997
    Co-Authors: Thomas Naumann, Matthias Kirsch, Michael Frotscher, Hans-dieter Hofmann
    Abstract:

    Using non-radioactive in situ hybridization we investigated the effect of Fimbria-Fornix transection on the expression of ciliary neurotrophic factor receptor α (CNTFRα) mRNA in axotomized septohippocampal neurons of the rat septal complex. Whereas CNTFRα expression was undetectable in the medial septal nucleus/diagonal band complex (MSDB) of control animals, specific up-regulation was observed in MSDB neurons after Fimbria-Fornix transection. CNTFRα expression was maximal 7–10 days after the lesion and had returned to control levels after 3 weeks. Following unilateral Fimbria-Fornix transection, CNTFRα up-regulation was restricted to the MSDB ipsilateral to the lesion. When cholinergic septal neurons were selectively eliminated by immunolesioning with 192 IgG-saporin prior to Fimbria-Fornix transection, the lesion-induced expression of CNTFRα was still observed in many medial septal nucleus neurons. These results demonstrate that after Fimbria-Fornix transection CNTFRα expression is transiently induced in axotomized, non-cholinergic neurons of the medial septal nucleus, suggesting a postlesion function of locally supplied CNTF.

  • Organization of identified fiber tracts in the rat Fimbria-Fornix: an anterograde tracing and electron microscopic study.
    Anatomy and embryology, 1996
    Co-Authors: G. Adelmann, Thomas Deller, Michael Frotscher
    Abstract:

    The fimbria is a major route for afferent and efferent fibers of the hippocampal formation. However, little is known about the intrinsic organization of the Fimbria-Fornix complex. In this study, the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHAL) was used to analyze the ultrastructure and topography of identified fiber tracts within the Fimbria-Fornix. Septo-hippocampal fibers are loosely distributed throughout the Fimbria-Fornix. Commissural fibers cross the midline in the ventral hippocampal commissure and form a tight fiber bundle in the fimbria. Crossed entorhino-hippocampal fibers cross the midline in the ventral hippocampal commissure rostral to the commissural fiber bundle, and crossed entorhino-entorhinal fibers pass through the dorsal hippocampal commissure. This suggests a topographical organization of fiber tracts within the Fimbria-Fornix that reflects the laminar organization of the hippocampal target structure: fibers of the diffusely terminating septohippocampal projection are loosely distributed throughout the Fimbria-Fornix, while those projections that are known to terminate in specific laminae of the hippocampal formation (commissural projection, crossed entorhino-hippocampal projection) form fiber bundles within the fimbria and the ventral hippocampal commissure.

  • Fate of GABAergic septohippocampal neurons after fimbria‐fornix transection as revealed by in situ hybridization for glutamate decarboxylase mRNA and parvalbumin immunocytochemistry
    The Journal of comparative neurology, 1995
    Co-Authors: P. Kermer, Thomas Naumann, Roland A. Bender, Michael Frotscher
    Abstract:

    Many septohippocampal neurons are GABAergic and are affected by transection of the Fimbria-Fornix, like the septohippocampal cholinergic cells. Here we have studied the changes that occur in GABAergic septohippocampal neurons following Fimbria-Fornix transection. For labeling of septohippocampal projection neurons, adult Sprague-Dawley rats received injections of the fluorescent tracer Fluoro-Gold into the hippocampus 1 week prior to bilateral transection of the Fimbria-Fornix. After axotomy, rats were allowed to survive for varying periods ranging from 3 weeks to 18 months. Following fixation of the animals, sections through the septal region were either stained by in situ hybridization for glutamate decarboxylase (GAD) mRNA or immunostained for parvalbumin (PARV) which is known to be present in GABAergic septohippocampal neurons. In situ hybridization for GAD mRNA revealed no statistically significant changes in cell number 3 weeks and 6 months postlesion. In contrast, PARV-immunoreactive neurons were reduced to 35% of control 3 weeks postlesion. This value increased to 66% after 6 months of survival. As seen in the electron microscope, axotomized PARV-positive neurons exhibited characteristics of vital cells. Most neurons contained lysosomes associated with Fluoro-Gold, resulting from retrograde labeling prior to Fimbria-Fornix transection. We conclude that mainly PARV-containing GABAergic neurons in the medial septal nucleus (MS) project to the hippocampus and are thus heavily affected by the lesion but are able to survive and restore the synthesis of PARV. The lack of significant changes in the number of GAD mRNA-expressing cells is explained by the presence of numerous GABAergic MS neurons not projecting to the hippocampus. © 1995 Wiley-Liss Inc.

  • Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after Fimbria-Fornix transection.
    The Journal of comparative neurology, 1994
    Co-Authors: Thomas Naumann, P. Kermer, Michael Frotscher
    Abstract:

    Most cholinergic projection neurons in the medial septal nucleus (MS) lose their capability to synthesize choline acetyltransferase (ChAT) after axotomy by bilateral Fimbria-Fornix transection. We have recently shown that identified septohippocampal neurons survive axotomy up to 10 weeks and display fine-structural characteristics of cells in control rats. However, the fate and functional role of these neurons remained unclear. Here we describe observations made in rats which survived axotomy for 6 months. Adult Sprague-Dawley rats were subjected to bilateral transection of the Fimbria-Fornix system. In some animals septochippocampal projection neurons were labeled by the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy. After varying survival times following Fimbria-Fornix transection, the animals were fixed and sections of the septal region immunostained for ChAT. Three weeks postlesion, the number of ChAT-positive cells in the MS was reduced to 19% of control, suggesting a severe neuronal loss. However, 10 weeks and 6 months after axotomy this value increased to 28% and 54%, respectively. Fine-structural analysis of ChAT-postive neurons after 6 months survial revealed all characteristics of vital cells including normal input synapses. The majority of these cells could be identified as former septohippocampal projection neurons by the presence of FG. We conclude that many neurons in the MS have the capacity to restore their transmitter synthesis in a long-lasting process following axotomy. © Wiley-Liss, Inc.