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Biomedical subjects

F S Roman

Publications and source records attributed to F S Roman.

At least 19 recordsLinked to original sources
PubMed2006

Involvement of tissue inhibition of metalloproteinases-1 in learning and memory in mice.

Tissue inhibitor of metalloproteinases (TIMP-1) is one of the four-member family (TIMPs-1-4) of multifunctional proteins that inhibit matrix metalloproteinases (MMPs). Its expression in the hippocampus is neuronal-activity-dependent and dramatically induced by stimuli leading to long-term potentiation (LTP), suggesting that TIMP-1 is a candidate plasticity protein potentially involved in learning and memory processes. We tested this hypothesis in a hippocampus-dependent task using the new olfactory tubing maze, with mice carrying a null mutation for TIMP-1 (TIMP-1 KO) and mice overexpressing TIMP-1 (TIMP-1 (tg)). The TIMP-1 KO mice were significantly impaired in making correct odor-reward associations when compared with their respective wild type (WT) littermates, while TIMP-1 overexpressing mice performed better than their WT controls. Both genetically modified mice learned the paradigm and the timing of the task, like their respective WTs, and no olfactory dysfunctioning was observed. These data suggest that TIMP-1 is involved in learning and memory processes related to the hippocampus, and support the hypothesis that the MMP/TIMP ratio, and hence MMP activity, modulates neuronal plasticity in normal learning and memory processes, while altered proteolytic activity could impair cognitive functions.

Animals↗
PubMed2006

Strain differences in rewarded discrimination learning using the olfactory tubing maze.

We trained BALB/c Byllco (C), CD-1, SV 129/SvPasCr1 (129 SV), C57BL/6 (B6) and DBA/2J (D2) mice using the olfactory tubing maze with the hope of gaining insight into behavioral genetics related to learning and memory processes. All strains of mice acquired the odor-reward associations using this new task except the D2 strain. The C, CD-1, and 129 SV consistently remembered the associations from the sixth 20-trial training session, reaching 80% +/- 5 correct responses in session seven. The B6 mice required one more session to reach 76%, while the D2 mice never learned the correct odor-reward associations. All mice learned the paradigm and the timing of the task, although the 129 SV mice decreased slower the inter-trial intervals across sessions. With this new task, D2 mice, with a deficit totally devoted to an impairment on learning and memory, can be used as a model of hippocampal dysfunction, in some respects like that observed in human amnesic patients whose selective hippocampal-dependent memory is deeply impaired. The high-scoring strains (C, CD-1, and 129 SV) seem to be ideal in this task to study a gene-targeting mutation postulated to reduce behavioral performance, and inversely, for D2 mice. The moderate-scoring strain, B6, should be ideal for allowing gene-targeting to go either way. In addition, this new task, which enables automated training of odor associations, could be used for studying the phenomenon of transitivity in mice, as described in rats.

Animals↗
PubMed2005

Selective impairment of subcategories of long-term memory in mice with hippocampal lesions accessed by the olfactory tubing maze.

A new apparatus, the olfactory tubing maze for mice, was developed recently to study learning and memory processes in mice in regard to their ethological abilities. As in humans, BALB/c mice with selective bilateral lesions of the hippocampal formation showed selective impairment of subcategories of long-term memory when tested with the olfactory tubing maze. After three learning sessions, control mice reached a high percentage of correct responses. They consistently made the olfactory-reward associations, but antero-dorsal and postero-ventral hippocampal-lesioned mice did not. However, all lesioned mice learned the paradigm and the timing of the task as fast and as well as control mice. These data suggest that the olfactory tubing maze can be used to study subcategories of memory, such as declarative and non-declarative memory, which are similar in some respects to those observed in humans. Consequently, possible memory effects of classical approaches (i.e., pharmacological or lesion studies) or genetic modifications in transgenic or gene-targeting mice can be effectively analyzed using this new apparatus.

Animals↗
PubMed2004

A novel experimental paradigm for studying cognitive functions related to delayed response tasks in mice.

Rodents are the animals most commonly employed to model human cognitive functions, but serious problems arise from the non-selective use of behavioral paradigms that measure different processes in rodents than those found in humans. To avoid problems stemming from the use of different paradigms on humans and mice, a new experimental paradigm for mice was developed to study the cognitive functions involved in delayed response tasks. The experiments were conducted in an olfactory tubing maze using three successive delayed response tasks: an alternation task, a non-alternation task, and a reversal task. Mice had to discover the rule by themselves by choosing one of two identical odor cues presented simultaneously at the left and right sides of a testing chamber. The success criterion was set at 10, 8, 6, or 4 consecutive correct responses, with a maximum of 80 trials per task, as used in primates. In the delayed alternation task with the criterion of 10 or 8 consecutive successful trials, the rule was discovered but required many more than 80 trials for most of the mice. With a criterion of 6 or 4, the mice were successful but twice as many trials were necessary to reach the criterion of 6 as opposed to 4. In the delayed non-alternation and reversal tasks, more than 80 trials were needed to figure out the new rule with the criterion of 10 or 8. All mice were successful with the criterion of 6 or 4. The results indicated that no matter what criterion was used, mice were able to discover the two rules on the three consecutive delayed response tasks, but they did so with more or less ease. This novel paradigm for mice should be useful in experiments on pharmacological treatments or for testing transgenic or gene-targeting mice to gain insight into the brain structures involved in this type of task.

Animals↗
PubMed2004

Modulation of memory processes and cellular excitability in the dentate gyrus of freely moving rats by a 5-HT4 receptors partial agonist, and an antagonist.

Firstly, olfactory association learning was used to determine the modulating effect of 5-HT4 receptor involvement in learning and long-term memory. Secondly, the effects of systemic injections of a 5-HT4 partial agonist and an antagonist on long-term potentiation (LTP) and depotentiation in the dentate gyrus (DG) were tested in freely moving rats. The modulating role of the 5-HT4 receptors was studied by using a potent, 5-HT4 partial agonist RS 67333 [1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone] and a selective 5-HT4 receptor antagonist RS 67532 [1-(4-amino-5-chloro-2-(3,5-dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1-propanone]. Agonist or antagonist systemic chronic injections prior to five training sessions yielded a facilitatory effect on procedural memory during the first session only with the antagonist. Systemic injection of the antagonist only before the first training session improved procedural memory during the first session and associative memory during the second session. Similar injection with the 5-HT4 partial agonist had an opposite effect. The systemic injection of the 5-HT4 partial agonist prior to the induction of LTP in the dentate gyrus by high-frequency stimulation was followed by a population spike increase, while the systemic injection of the antagonist accelerated the depotentiation 48 h later. The behavioural and physiological results pointed out the involvement of 5-HT4 receptors in processing related to the long-term hippocampal-dependent memory system, and suggest that specific 5-HT4 agonists could be used to treat amnesic patients with a dysfunction in this particular system.

Aniline Compounds↗
PubMed2002

The olfactory tubing maze: a new apparatus for studying learning and memory processes in mice.

In order to have an ethologically relevant behavioral task, we developed the olfactory tubing maze to study learning and memory processes in mice. Mice have to make two olfactory-reward associations across three training sessions. The maze is made up of four identical testing chambers connected to each other by semicircular cylinders. After having chosen one of two odors presented on each side of a testing chamber, the mice have to run to the next testing chamber. From one testing chamber to the next, the side for presentating each odor is randomly assigned. The mouse must run through the entire circular maze to make a response at the four testing chambers. A complete session consists of 20 trials made by running five times clockwise through the maze with 4 trials per run. The training and data recording are fully automated by a custom-made software program. Three different experiments were performed. The results indicated that mice can easily make the olfactory discriminative associations in this new apparatus. Analysis of the data suggests that it would be possible using this olfactory tubing maze to study sub-categories of memory similar in some respects to those observed in humans. Consequently, possible effects on learning and memory of classical treatments (i.e. pharmacological or lesions) or genetic modifications in transgenic or gene-targeting mice could be tested.

Animals↗
PubMed2002

Learning and memory of cue-reward association meaning by modifications of synaptic efficacy in dentate gyrus and piriform cortex.

This article begins with a review of recent experiments investigating the synaptic efficacy changes occurring in rat dentate gyrus and piriform cortex during an associative olfactory task. In all these experiments, animals were trained to discriminate among an artificial cue, a patterned electrical stimulation distributed to the lateral olfactory tract associated with a water reward, and a natural odor associated with a flash of light. Monosynaptic field potential responses evoked by single electrical stimuli to the lateral olfactory tract were recorded in the ipsilateral piriform cortex before and just after each training session. Monosynaptic field and polysynaptic field potentials evoked by single electrical stimuli applied respectively to the lateral perforant pathway and lateral olfactory tract were also recorded in ipsilateral dentate gyrus. The results showed an increase in synaptic efficacy subsequent to the first training session in the dentate gyrus network when compared with piriform cortex at the later stage of the learning. The early increase of monosynaptic response in the dentate gyrus was observed immediately after the first learning session but disappeared 24 h later. Inversely, a synaptic depression developed across sessions, becoming significant at the onset of the last (fifth) session. The polysynaptic potential recorded in this structure increased substantially when rats began to discriminate the leaming cues, usually after the second or third learning session. Then, from the third to the fifth session, an LTP like-phenomenon appeared in piriform cortex when rats perfectly mastered the associations. Experiments using high-frequency stimulation to prevent changes in gyrus dentatus indicated that the onset of the observed depression was necessary for the learning of the olfactory associations. The fact that hippocampal and cortical neuronal networks exhibited different timing in synaptic efficacy changes could physiologically explain learning and memory processes.

Animals↗
PubMed2002

Early integrative processes physiologically observed in dentate gyrus during an olfactory associative training in rat.

Modifications of synaptic efficacy in the dentate gyrus were investigated during an olfactory associative task. A group of rats was trained to discriminate between a patterned electrical stimulation of the lateral olfactory tract, used as an artificial cue, associated with a water reward, and a natural odor associated with a flash of light. Monosynaptic field potential responses evoked by single electrical stimuli to the lateral perforant path were recorded in the granular layer of the ipsilateral dentate gyrus prior to and just after each training session. An early increase in this response was observed just after the first learning session but disappeared 24 hours later. Inversely, a synaptic depression developed across sessions, becoming significant at the onset of a last (fifth) session. When a group of naive animals was pseudo-conditioned, no increase was observed and the synaptic depression was noted since the onset of the second session. In a group of rats similarly trained for only one session, and in which EPSPs were recorded throughout the 24 hours that followed, it was demonstrated that the increase lasted at least two hours, while the significant synaptic depression started after the fourth hour. These results are consistent with the early involvement of the dentate gyrus in learning the association between the cues and their respective rewards. These early integrative processes physiologically observed in dentate gyrus suggest early hippocampal processing before dentate gyrus reactivation via entorhinal cortex which will allow long-term memory storage in cortical areas once the meaning of the olfactory cues is learned.

Animals↗
PubMed2000

Differential modulation of the 5-HT(4) receptor agonists and antagonist on rat learning and memory.

Recent data suggest that activation of 5-HT(4) receptors may modulate cognitive processes such as learning and memory. In the present study, the effects of two potent and selective 5-HT(4) agonists, RS 17017 [1-(4-amino-5-chloro-2-methoxyphenyl)-5- (piperidin-1-yl)-1-pentanone hydrochloride] and RS 67333 [1(4-amino-5-chloro-2-methoxyphenyl)-3- (1-n-butyl-4-piperidinyl)-1-propanone], were studied in an olfactory associative discrimination task. The implication of 5-HT(4) receptors in the associative discriminative task was suggested by the following observation. Injection of a selective 5-HT(4) receptor antagonist RS 67532 [1-(4-amino-5-chloro-2-(3, 5-dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1-pentanone; 1 mg/kg: i.p.] before the third training session induced a consistent deficit in associative memory during the following training sessions. This deficit was absent when the antagonist was injected together with either a specific hydrophilic 5-HT(4) (RS 17017, 1 mg/kg) or a specific hydrophobic (RS 67333, 1 mg/kg) 5-HT(4) receptor agonist. RS 67333 was more potent than RS 17017. This difference in potency certainly reflects a difference in their capacity to enter into the brain. This is also likely to be the reason why, injected alone, the hydrophobic 5-HT(4) agonist (RS 67333) but not the hydrophilic 5-HT(4) agonist (RS 17017) improved learning and memory performance.

Aniline Compounds↗
PubMed1999

Correlations between electrophysiological observations of synaptic plasticity modifications and behavioral performance in mammals.

Within the past century it has been well established that most mature neurons lose their ability to divide. Since then, it has been assumed that behavioral performance leads to synaptic changes in the brain. The existence of these potential changes has been demonstrated in numerous experiments, and different mechanisms contributing to synaptic plasticity have been discovered. Many structures involved in different types of learning have now been identified. This article reviews the different methods used with mammals to detect electrophysiological modifications in synaptic plasticity following behavior. Evidence of long-term potentiation and long-term depression has been found in the hippocampus and cerebellum, respectively, and empirical data has been used to correlate these mechanisms with specific learning performance. Similar observations were made recently in the septum and amygdala. These phenomena seem to be involved in maintaining the performance in the cortical areas of the brain. Ongoing attempts to find the relationship between behavioral performance and modifications in synaptic efficacy allow to speculate upon the dynamics of cellular mechanisms that contribute to the ability of mammals to modify wide neuronal networks in the brain during their life.

Animals↗
PubMed1999

Early polysynaptic potentiation recorded in the dentate gyrus during an associative learning task.

In this report, we investigated the electrophysiological dynamics of the neuronal circuit including the dentate gyrus during an associative task. A group of rats was trained to discriminate between a patterned electrical stimulation of the lateral olfactory tract, used as an artificial cue associated with a water reward, and a natural odor associated with a light flash. Polysynaptic field potential responses, evoked by a single electrical stimulation of the same lateral olfactory tract electrode, were recorded in the molecular layer of the ipsilateral dentate gyrus prior to and just after each training session. An increase in this response was observed when a significant discrimination of the two cues began. A positive correlation was found between the change in the polysynaptic potentiation and behavioral performances. The onset latency of the potentiated polysynaptic response was 35-45 ms. When a group of naive animals was pseudoconditioned, no change in field potential was observed. These results are consistent with the hypothesized dynamic activation of the dentate gyrus early in the making of association, allowing gradual storage of associative information in a defined set of synapses. Moreover, the onset latency of the potentiated response suggests the existence of reactivating hippocampal loops during the processing of associative information.

Analysis of Variance↗
PubMed1997

Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

Animals↗
PubMed1997

Neonatal gamma-ray irradiation impairs learning and memory of an olfactory associative task in adult rats.

Adult neonatally gamma-irradiated rats were compared with control animals in a non-spatial olfactory associative task using two different procedures. Irradiation induced a clear reduction in the total mean area of the olfactory bulbs and hippocampus but not of the orbital prefrontal cortex, diagonal band and cell layers of the entorhinal and piriform cortex. The gamma-irradiation affected the granule cells of the olfactory bulbs and differentially altered the cell layers of the subfields of the ammonic fields and the dorsal and ventral blades of the dentate gyrus. In the CA1 ammonic field, dorsal and ventral blades of the dentate gyrus, the cellular loss was significant in comparison with control adult rats. The behavioural data indicated that irradiated rats were deeply disturbed in learning the odour-reward association, and substantially impaired in a reversal experiment, but not in the discrimination of the odours per se. The cellular loss in the olfactory bulbs, in the CA1 and in the ventral blade of the gyrus dentatus was positively correlated with the deficit in behavioural performance. The data support the findings that the hippocampal system participates in the odour-reward associations and facilitates the long-term storage of associations after learning is achieved in this olfactory associative task.

Animals↗
PubMed1996

Modulation of synaptic plasticity in the hippocampus and piriform cortex by physiologically meaningful olfactory cues in an olfactory association task.

Animals were trained to discriminate two natural odors while another group was trained to discriminate between a patterned electrical stimulation distributed on the lateral olfactory tract (LOT), labelled olfaco-mimetic stimulation (OMS), used as an olfactory cue versus a natural odor. No statistically significant difference was observed in behavioral data between these two groups. The animals trained to learn the meaning of the OMS exhibited a gradual long-term potentiation (LTP) phenomenon in the piriform cortex. When a group of naive animals was pseudo-conditioned, giving the OMS for the the same number of sessions but without any olfactory training, no LTP was recorded. These results indicate that the process of learning olfactory association gradually potentiates cortical synapses in a defined cortical terminal field, and may explain why LTP in the piriform cortex is not elicited by the patterned stimulation itself, but only in and associative context. As olfactory and hippocampus regions are connected via the lateral entorhinal cortex, the olfac-omimetic model was used to study the dynamic of involvement of the dentate gyrus (DG) in learning and memory of this associative olfactory task. Polysynaptic field potentials, evoked by the LOT stimulation, were recorded in the molecular layer of the ipsilateral DG. An early and rapid (2nd session) potentiation was observed when a significant discrimination of the two cues began to be observed. The onset latency of the potential response was 30-40 ms. When a group of naive animals was pseudoconditioned, no change was observed. Taken together, these results support the hypothesis that early activation of the DG during the learning of olfactory cue allows the progressive storage of olfactory information in a defined set of potentiated cortical synapses. The onset latency of the polysynaptic potentiated responses suggests that existence of reactivating hippocampal loops during the processing of olfactory information.

Animals↗
PubMed1993

Long-term potentiation in rat piriform cortex following discrimination learning.

The behavioral conditions for induction of long-term potentiation (LTP) elicited by unilateral patterned electrical stimulation of the lateral olfactory tract (LOT) was studied in piriform cortex. A group of animals was trained to discriminate two natural odors while another group was trained to discriminate a patterned stimulation (bursts of 4 pulses at 100 Hz repeated at 160-ms intervals) used as an olfactory cue, versus a natural odor. Both groups were successful in the discrimination and no statistical significant difference was observed in behavioral data between these two groups on series of 5 successive daily training sessions. With animals trained to perform the task with the artificial cue, monosynaptic responses evoked by single pulse stimulation of the LOT were collected, prior to and just after each of the successive training sessions. Comparisons with behavioral data collected at the beginning and the end of a training session revealed that the population synaptic responses increased with the percentage of correct responses performed by the animals. This increase (LTP) was progressive and present only when significant discrimination between the two cues was observed. A positive correlation was found between the increase in monosynaptic responses and the level of performance. Responses elicited by control electrodes were slightly depressed at the end of the discrimination learning series. In addition, when a group of naive animals was pseudoconditioned, giving the patterned electrical stimulation for the same number of sessions but without any olfactory training, no LTP was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Learning and memory of odor-reward association: selective impairment following horizontal diagonal band lesions.

Rats with horizontal diagonal band of Broca (HDBB) lesions were trained in a successive-cue olfactory discrimination using different intertrial intervals (ITIs). They learned the paradigm of the task, but substantial impairment in performance of odor-reward associations was observed when the ITIs were longer than 15 s. They performed as well as control animals with short ITIs when they were trained previously with long ITIs, but forgetting appeared very soon thereafter (24 hr later). The finding is that the HDBB is an essential relay between the hippocampal system and the olfactory cortex: The HDBB allows associative memory storage when a limited-duration short-memory system located elsewhere is overloaded.

Animals↗
PubMedDate not supplied

Age-related learning and memory deficits in odor-reward association in rats.

In these experiments, potential cognitive deficits in aged rats were studied using an odor-reward association task. Aged Fischer 344 rats first performed to an odor-reward association task. After five daily sessions of 60 trials, the aged rats were globally impaired in comparison to the control rats. However, considering individual performance, 40% of the aged population performed as well as the control animals. These aged rats were then tested for retention at various times. They demonstrated an increased rate of forgetting which was confirmed by a final reversal experiment. The other group of aged rats remained severely impaired and unable to make the odor-reward association correctly until the inter-trial interval was decreased from 15 to 5 s. When they were submitted to a task requiring the learning and retention of 7 new odor pairs, these aged rats again performed poorly. A subsequent reversal session confirmed the rapid forgetting phenomenon for this aged group, even when the odor-reward associations were in fact made.

Aging↗