T Durkin

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (41)136.71 Total impact

  • Bruno Bontempi, Thomas P. Durkin
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    ABSTRACT: Both clinical studies and experiments in animals have provided evidence for the existence of a temporally graded retrograde amnesia following lesions of the medial temporal lobe, including the hippocampus. This form of amnesia, which is characterized by a loss of memory for recent events acquired prior to the onset of amnesia while more remote memories are preserved, is one of the major arguments for the existence of a consolidation process necessary for stable, long-term memory formation. It is now well established that the formation of declarative memory (memories for facts and events) involves changes in synaptic plasticity within the medial temporal lobe. However, our group and others have demonstrated that the hippocampus has only a time-limited role in long-term memory storage of certain types of information, such that extrahippocampal structures, namely cortical regions, eventually become capable of supporting the retrieval of remote memories independently. In other words, the hippocampus does not store remote memories, yet what happens beyond the hippocampus remains unclear. This issue has been the subject of intense investigation and debate in the field of cognitive neuroscience, but to date, no convincing evidence as to the identity, mechanisms and putative interactions between memory systems underlying remote memory storage and retrieval have clearly emerged. To address this issue, we have conducted brain imaging experiments using (14C)2-deoxyglucose mapping and analyses of changes in the expression of activity-dependent genes (c-fos and Zif268) in mice submitted to recent and remote spatial memory testing. Our findings show that memory processing and consolidation require a time-dependent hippocampal-cortical dialogue, ultimately enabling structured cortical networks to mediate recall and use of cortically stored remote memories independently. However, the cortex does not simply serve as a passive storage site but may also actively integrate new memories depending on the organization and status of pre-existing knowledge. The prefrontal cortex in particular appears to play a crucial role in integrating and binding information from distributed cortical networks and in modulating the level of hippocampal activation during memory recall. These findings are discussed in the context of current models of memory consolidation and in light of data from the recent literature in humans and animals.
    04/2007: pages 19-39;
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    ABSTRACT: The hippocampus is crucial for spatial memory formation, yet it does not store long-lasting memories. By combining functional brain imaging and region-specific neuronal inactivation in mice, we identified prefrontal and anterior cingulate cortices as critical for storage and retrieval of remote spatial memories [correction]. Imaging of activity-dependent genes also revealed an involvement of parietal and retrosplenial cortices during consolidation of remote memory. Long-term memory storage within some of these neocortical regions was accompanied by structural changes including synaptogenesis and laminar reorganization, concomitant with a functional disengagement of the hippocampus and posterior cingulate cortex [correction]. Thus, consolidation of spatial memory requires a time-dependent hippocampal-cortical dialogue, ultimately enabling widespread cortical networks to mediate effortful recall and use of cortically stored remote memories independently.
    Science 08/2004; 305(5680):96-9. DOI:10.1126/science.1098180 · 31.48 Impact Factor
  • T Maviel, T P Durkin
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    ABSTRACT: A delayed-matching spatial working memory protocol in a 5-arm maze was used to test the hypothesis of differential roles for central nicotinic and muscarinic cholinergic receptors in mediating task performance. In experiment 1, using a within subjects-repeated design, groups of C57Bl/6 mice, previously trained to criterion with a 4 h retention interval separating presentation and test phases, received i.p. injections of either saline, scopolamine (0.8 mg/kg), mecamylamine (8.0 mg/kg), or the combination of scopolamine and mecamylamine before re-testing. Injections were given either, a) 15 min pre-presentation or, b) 30 s, c) 15 min, d) 3 h 45 min post-presentation in order to differentially affect the acquisition, trace maintenance and recall phases. Significant decreases in correct responses were observed for each drug treatment but the effects were a function of the time of treatment. Results of condition d), (i.e.15 min before retention test) confirm previous reports of severe disruption by each antagonist and their combination on retention. However, conditions a-c) show a constant disruption by scopolamine, increasing disruption by mecamylamine, whereas the combined treatment was without effect. Although the data show that central nicotinic and muscarinic antagonists both modulate working memory performance, they indicate first, that scopolamine-induced "amnesia" results, not from selective post-synaptic M1 muscarinic blockade but from indirect over-activation of nicotinic receptors. Second, the observation of high levels of retention although nicotinic and muscarinic receptors had undergone combined blockade during a large part of the retention interval is incompatible with the concept that test-induced activation of central cholinergic neurones mediates memory trace maintenance. Finally, taken with data from experiment 2, using a short (20 min) treatment-to-test interval, we conclude that central nicotinic receptors play a key role in attentional processes enabling working memory trace access during retrieval.
    Neuroscience 02/2003; 120(4):1049-59. DOI:10.1016/S0306-4522(03)00403-2 · 3.33 Impact Factor
  • Vincent David, Thomas P Durkin, Pierre Cazala
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    ABSTRACT: The involvement of dopamine neurotransmission in opiate reward remains controversial. To investigate the dopaminergic basis of opiate reward by comparing the effect of systemic injection of the D2/D3 antagonist sulpiride on morphine self-administration (ICSA) into the ventral tegmental area (VTA) or the nucleus accumbens (NAc) BALB/c mice were unilaterally implanted with a guide cannula 1.5 mm above either the VTA or the NAc. On experimental days, a stainless-steel injection cannula was inserted via the guide cannula, and mice were trained to discriminate the arm of a Y-maze reinforced by intracranial morphine microinjections (6.5 pmol or 65 pmol/50 nl) from the neutral arm (no injection). Following acquisition of morphine ICSA, the dopamine D2/D3 receptor antagonist sulpiride (50 mg/kg, i.p.) was administered 30 min before testing. Sulpiride produced an extinction of intra-VTA, but not intra-NAC, morphine self-administration. Extinction in VTA subjects was followed by a re-appearance of ICSA, although mice continued to receive sulpiride injections. Extinction was re-induced when the dose of sulpiride was raised to 100 mg/kg, whereas no effect of this dose was detected on intra-NAc self-administration. Maintenance of intra-VTA, but not intra-NAc, morphine self-administration depends acutely on D2/D3 receptors. However, the deleterious effect of sulpiride on intra-VTA morphine self-administration is transient. Reappearance of ICSA under neuroleptic treatment in VTA subjects may be related to the sensitization effect of intra-VTA morphine infusions, combined with an upregulation of D2/D3 receptors and alterations of DA metabolism by repeated sulpiride injections.
    Psychopharmacology 04/2002; 160(3):307-17. DOI:10.1007/s00213-001-0981-2 · 3.99 Impact Factor
  • Vincent David, Thomas P. Durkin, Pierre Cazala
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    ABSTRACT: Rationale: The involvement of dopamine neurotransmission in opiate reward remains controversial. Objective: To investigate the dopaminergic basis of opiate reward by comparing the effect of systemic injection of the D2/D3 antagonist sulpiride on morphine self-administration (ICSA) into the ventral tegmental area (VTA) or the nucleus accumbens (NAc) Methods: BALB/c mice were unilaterally implanted with a guide cannula 1.5mm above either the VTA or the NAc. On experimental days, a stainless-steel injection cannula was inserted via the guide cannula, and mice were trained to discriminate the arm of a Y-maze reinforced by intracranial morphine microinjections (6.5pmol or 65pmol/50nl) from the neutral arm (no injection). Following acquisition of morphine ICSA, the dopamine D2/D3 receptor antagonist sulpiride (50mg/kg, i.p.) was administered 30min before testing. Results: Sulpiride produced an extinction of intra-VTA, but not intra-NAC, morphine self-administration. Extinction in VTA subjects was followed by a re-appearance of ICSA, although mice continued to receive sulpiride injections. Extinction was re-induced when the dose of sulpiride was raised to 100mg/kg, whereas no effect of this dose was detected on intra-NAc self-administration. Conclusion: Maintenance of intra-VTA, but not intra-NAc, morphine self-administration depends acutely on D2/D3 receptors. However, the deleterious effect of sulpiride on intra-VTA morphine self-administration is transient. Reappearance of ICSA under neuroleptic treatment in VTA subjects may be related to the sensitization effect of intra-VTA morphine infusions, combined with an upregulation of D2/D3 receptors and alterations of DA metabolism by repeated sulpiride injections.
    Psychopharmacology 02/2002; 160(3):307-317. · 3.99 Impact Factor
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    ABSTRACT: A 5-arm maze was used to measure sustained visuo-spatial attention in C57Bl/6 mice and test the hypothesis of differential functional roles for central nicotinic and muscarinic receptors in mediating task performance. Mice were first trained to acquire the basic visual discrimination task in which, on each trial, one randomly chosen arm among the five open arms was baited and remained lit until an arm-choice was made. Mice were then submitted to attentional testing in which trials using light signals of 2, 1 or 0.5 s were intermixed to evaluate the decrement in correct responses as a function of the decrease in light signal duration and thus, to construct a reference curve for the attentional performance of C57Bl/6 mice. Mice were then divided into four groups and received, in rotation, over four pharmacological sessions according to a Latin-square design, i.p. injections of either mecamylamine (4.0 mg/kg), scopolamine (0.8 mg/kg), the combination of mecamylamine and scopolamine or saline, 20 min before re-testing. Injection of cholinergic antagonists produced decreases in percentage of correct responses, which were systematically associated with significant increases in choice latencies. Mecamylamine produced slight disruption, whereas scopolamine and the combined treatment both produced severe disruption. In conclusion, whereas both nicotinic and muscarinic cholinergic antagonists disrupt performance in the attentional task, the increase in response latencies entails that correct responding becomes more dependent on the working memory processes and thus compromises conclusions as to a selective disruption of attention.
    Behavioural Brain Research 02/2002; 128(1):91-102. DOI:10.1016/S0166-4328(01)00306-0 · 3.39 Impact Factor
  • T P Durkin, C Beaufort, L Leblond, T Maviel
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    ABSTRACT: A 5-arm maze has been developed to provide parallel tests of sustained visuo-spatial attention and spatial working memory in mice. C57Bl/6 mice were trained to select, either by immediate response (attention) or by delayed-matching response (working memory), one target arm among the five open arms. For attention testing, mice were first trained to acquire the basic task in which one randomly selected baited arm remained lit until a choice was made. Criterion of >80% correct with a response latency <5 s was attained in 52-56 trials. Following this, attention was tested by using trials wherein light signal durations of 2, 1 or 0.5 s were intermixed to vary attentional load. In the working memory test, mice were submitted to a forced visit to a randomly selected baited arm during a presentation phase. Following a variable retention interval (R.I.), mice were replaced into the maze and rewarded for choosing this arm. Criterion of >80% correct was attained in 35-40 trials and mice exhibited high levels of retention for R.I.s up to 4 h. Results validate the 5-arm maze for evaluation of both sustained visuo-spatial attention and spatial working memory in mice. Both the tasks are rapidly acquired and the 20% chance level provides high resolution for evaluating performance. This comparative strategy allows to dissociate attention and memory and to reveal deficits in these processes during ageing or in knockout strains. The high level of retention performance over R.I.s of 4 h enables studies using pharmacological treatments differentially affecting the acquisition, encoding, retention or retrieval phases of working memory. Furthermore, functional brain imaging studies may be used to identify neuronal networks which are differentially activated during these distinct phases.
    Behavioural Brain Research 12/2000; 116(1):39-53. DOI:10.1016/S0166-4328(00)00248-5 · 3.39 Impact Factor
  • T. P. Durkin, C. Beaufort, T. Maviel, L. Leblond
    Journal of Physiology-Paris 10/1998; 92(5):427-428. DOI:10.1016/S0928-4257(99)80040-0 · 2.35 Impact Factor
  • Vincent David, Thomas P. Durkin, Pierre Cazala
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    ABSTRACT: In order to study the functional role of the trans-synaptic neuronal interaction between glutamatergic afferents and mesolimbic dopaminergic neurons in internal reward processes, BALB/c male mice were unilaterally implanted with a guide-cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the following experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self-administration behaviour of either the competitive N-methyl-D-aspartate antagonist, D(-)-2-amino-7-phosphonoheptanoic acid (AP-7) or the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (3 ng/50 nL) using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a microinjection of either of these glutamatergic antagonists and the neutral arm of the maze, and a robust self-administration of either of these compounds was observed from the first session of acquisition. These data provide strong evidence that the intra-VTA microinjection of either of these subclasses of glutamatergic antagonist produces an effect which is interpreted centrally by the experimental subjects as being highly rewarding. Once the self-administration response had been fully acquired by the experimental subjects, preinjection of the dopaminergic D2 antagonist, sulpiride (50 mg/kg i.p.), 30 min before the test, produced a rapid extinction of the self-administration response. This latter result demonstrates the dopaminergic D2 receptor dependence of this intra-VTA self-administration of both of these subclasses of glutamatergic antagonist. We conclude that the different glutamatergic afferent neuronal inputs to the VTA globally exert, in vivo, via the mediation of interposed endogenous GABAergic interneurons, a tonic trans-synaptic inhibitory regulation of neuronal activity in the mesolimbic dopaminergic pathway and that this complex neuronal interaction in the VTA plays a significant functional part in the modulation of internal reward processes.
    European Journal of Neuroscience 05/1998; 10(4):1394-402. DOI:10.1046/j.1460-9568.1998.00150.x · 3.67 Impact Factor
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    ABSTRACT: We previously reported that a human insulin transgene was specifically expressed in the medial habenula of the adult mouse brain, and that this expression was ascribed to the delta-168 transgene. The present study analyses the possible behavioural consequences of this insulin transgene expression using measures of food intake, spontaneous activity, emotional reactivity, learning and extinction performance of an operant task. The delta-168 transgenic mice did not differ from the C57BL/6 control mice as concerns food intake, behaviour in the open field, or emotional response in an elevated plus maze. On the other hand, measures of locomotor activity in a circular corridor revealed a significantly faster decline of spontaneous locomotor activity in male as compared to female delta-168 transgenic mice. Moreover, as compared to female transgenic mice, male transgenic mice exhibited a deficit in the rate of acquisition and an acceleration of the rate of extinction of a bar press response in a Skinner box. In contrast, the behaviour of female transgenic mice did not differ from either male or female C57BL/6 control mice. The results of the present study demonstrate that the behavioural modifications observed in delta-168 transgenic mice are sex-linked and suggest that these behavioural differences result from changes in the interaction (interface) between motivational and motor mechanisms mediated via the striato-habenulo-mesencephalic system.
    Behavioural Brain Research 01/1998; 89(1-2):259-66. DOI:10.1016/S0166-4328(97)00071-5 · 3.39 Impact Factor
  • V David, Thomas P. Durkin, Pierre Cazala
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    ABSTRACT: BALB/c mice were unilaterally implanted with a guide cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self-administration of a low dose (1.5 ng/50 nl) of bicuculline, a GABAA-antagonist, using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a micro-injection of bicuculline and the neutral arm of the maze, and robust self-administration of this GABAergic antagonist was observed. Once this self-administration response for bicuculline had been fully acquired, the systemic injection of the dopaminergic D2 antagonist sulpiride (50 mg/kg), 30 min before the test, produced a rapid extinction of the self-administration response. Moreover, if this same sulpiride pretreatment was given during the initial acquisition period mice did not discriminate between the two arms of the Y-maze. These data demonstrate the dopamine D2 dependence of this bicuculline self-administration behavior, and confirm that GABAergic interneurons and/or inputs normally transynaptically inhibit neuronal activity in the mesocorticolimbic dopamine system.
    Psychopharmacology 04/1997; 130(2):85-90. DOI:10.1007/s002130050214 · 3.99 Impact Factor
  • T P Durkin
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    ABSTRACT: Previous direct neurochemical studies of the temporal dynamics of cholinergic activation in the septohippocampal and nucleus basalis magnocellularis-cortical pathways at various stages during repeated testing of mice with selective spatial reference or working memory protocols [Durkin and Toumane (1992), Behav. Brain Res. 50, 43-52] showed that the post-test durations of cholinergic activation in each pathway varied as a function of the type of memory tested and the level of task mastery. Since (i) the hippocampal formation is considered to constitute a critical component of a temporary memory buffer, and (ii) working memory items are not thought to be submitted to consolidation and permanent storage, we postulated that the duration of testing-induced cholinergic activation in the septohippocampal pathway may govern the maintenance of the working memory trace over the retention interval. In order to test directly this hypothesis C57 B1/6 mice were extensively trained (one trial/day, 25-30 days) on an identical selective working memory task to attain high levels of retention (> 80% correct), but using either 5 min (Group 1), or 60 min (Group 2) retention intervals. At various times (30 s-75 min) following the initial acquisition phase of the test, cholinergic activity in the hippocampus and frontal cortex was quantified using measures of high-affinity choline uptake. Whereas cholinergic activation was observed in both pathways at 30 s post-acquisition and throughout the 5 min retention interval in Group 1, the situation in Group 2 is different, activation of the septohippocampal pathway being maintained for only 15 min, while activation in the nucleus basalis magnocellularis-cortical pathway is maintained for the totality of the 1 h retention interval. The nucleus basalis magnocellularis-cortical cholinergic pathway, in addition to its role in long-term reference memory storage processes may, thus, via an intervention in the temporal encoding of information, also subsume a complementary intermediate-term buffer storage role in working memory situations requiring retention intervals in excess of 15 min in mice. This secondary, "backup", function of the nucleus basalis magnocellularis-cortical pathway would thus liberate the septohippocampal complex from its primary active role in the temporary maintenance and/or accessibility of the working memory trace in these particular cases requiring long retention intervals.
    Neuroscience 11/1994; 62(3):681-93. DOI:10.1016/0306-4522(94)90469-3 · 3.33 Impact Factor
  • Abdoulaye Toumane, Thomas P. Durkin
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    ABSTRACT: The time course for vulnerability to the amnestic effects of the cholinergic antagonist, scopolamine, during the postacquisition period has been investigated. We have examined the effects of post-test injections of scopolamine (1 mg/kg ip) given at different times from 30 s for up to 6 h following the end of the first acquisition session of a concurrent spatial discrimination (reference memory) protocol in an 8-arm radial maze on subsequent long-term (24 h) retention performance in C57BL/6 mice. Results show that the immediate (30 s) post-test injection of scopolamine-HCl on Day 1 produces marked perturbation (amnesia) of long-term retention as attested to by significant deficits in various indices of spatial discrimination performance gain on Day 2 as compared to control subjects injected either with scopolamine-MBr or saline. The severity of this scopolamine-induced amnesia declines only slightly as a function of the treatment period 30 s-3 h post-test. However, no evidence for amnesia is observed if scopolamine-HCl injections are delayed for 6 h postsession. This important latter observation attests to the absence of any significant proactive effects of scopolamine on the ability of mice to perform the retention test via possible long-term effects on attention, motivation, or locomotor performance. These results thus constitute evidence for the existence of a limited (30 s-3 h) time gradient for vulnerability of the early memory trace to disruption by scopolamine. The present results are discussed in relation to our previous direct neurochemical observations describing the differential time courses of intervention of the ascending septohippocampal and nBM-cortical cholinergic pathways in the postlearning period. In particular, the presently observed time window concerning post-test vulnerability to scopolamine-induced amnesia corresponds more closely to the time course of the acute activation of the nBM-cortical cholinergic pathway, induced by testing with the same spatial memory protocol as used in the present study in mice.
    Behavioral and Neural Biology 10/1993; 60(2):139-51. DOI:10.1016/0163-1047(93)90243-B
  • Thomas P. Durkin
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    ABSTRACT: A neurochemical study of the transsynaptic interactions established between septal GABAergic interneurones and cholinergic septo-hippocampal neurones was conducted using mice. The effects of acute in vivo injections of either muscimol (20-500 ng/0.2 microliter), bicuculline (100 ng-1 micrograms/0.2 microliter) or saline vehicle (0.2 microliter) into the medial septum on septo-hippocampal cholinergic activity were evaluated using measures of hippocampal high affinity choline uptake at 30 min post-injection in two main groups of mice. The first (quiet control) remained in their home cages during the post-injection period whereas the second (active) were submitted, 10 min following injection to a 20-min period of spatial working memory testing in an 8-arm radial maze. Intraseptal injections of either muscimol or bicuculline produced significant (25-50%) inhibition of hippocampal cholinergic activity in quiet conditions (basal) as compared to intact or saline-injected mice. In the active groups, whereas memory testing induced significant cholinergic activation (+15-20%) in intact and saline injected mice at 30 s post-test no significant memory testing-induced activation was observed in either muscimol or bicuculline-injected mice at any dose. The role of septal GABAergic interneurones in the indirect transsynaptic control over the basal and activated states of septo-hippocampal cholinergic activity is discussed with respect to the concept that these complex neuronal interactions contribute to the physiological mechanisms involved in the modulation of working memory performance.
    Behavioural Brain Research 10/1992; 50(1-2):155-65. DOI:10.1016/S0166-4328(05)80297-9 · 3.39 Impact Factor
  • Thomas P. Durkin, Abdoulaye Toumane
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    ABSTRACT: We previously showed that the initial acquisition session of a spatial discrimination (mixed reference/working memory) test in an 8-arm radial maze induced differential activations in the ascending cholinergic septo-hippocampal and nBM-cortical pathways in mice. This data showed that the duration of post-test cholinergic activation was longer in the nBM-cortical pathway than in the septo-hippocampal projection. Moreover, the post-test durations but not the immediate post-test amplitudes of activation in each pathway decreased progressively as a function of repeated daily acquisition sessions. In the present study we have thus tested the hypotheses that the time-courses of post-test cholinergic activation in the septo-hippocampal and nBM-cortical pathways may vary both as a function of the type of memory used (working vs. reference) and according to the duration of repeated daily testing. Cholinergic activity in vivo in the hippocampus or frontal cortex of mice was quantified using measures of sodium-dependent high-affinity choline uptake at two different times (30 s and 15 min) following specific spatial working or reference memory testing in an 8-arm radial maze. The memory tests were administered daily over a 13-day period to attain high levels of performance in each type of task. In comparison to control groups both types of memory testing induced significant post-test cholinergic activations in each brain region on Day 15. However, cholinergic activity remained elevated in frontal cortex at 15 min post-test following reference memory testing, whereas significantly shorter durations of cortical and hippocampal cholinergic activation were observed following working memory testing using short (1 min) retention intervals. The possible significance of these differential modifications to the time-course of the post-test activations in these cholinergic pathways in working and reference memory processes and the putative transsynaptic mechanisms involved are discussed.
    Behavioural Brain Research 10/1992; 50(1-2):43-52. DOI:10.1016/S0166-4328(05)80286-4 · 3.39 Impact Factor
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    ABSTRACT: Behavioural studies in both humans and animals have shown that an acute rise in circulating glucose levels at or around the time of training enhances subsequent retention performance and can also afford protection from the amnesia produced by posttraining injections of scopolamine. In an attempt to directly investigate the neurochemical basis for these effects of glucose we have tested the hypothesis that raised glucose levels may enhance acetylcholine (ACh) synthesis and release in the brain during conditions of increased neuronal activity, induced either by training or pharmacological challenge, via a microdialysis study using rats. Microdialysate concentrations of ACh overflow from the hippocampus of fasted rats induced by i.p. injections of scopolamine (1 mg/kg) combined with concurrent s.c. injections of either glucose (2 g/kg) or saline were compared in successive 15-min samples using an on-line HPLC system. Scopolamine injections resulted in an immediate 10-20-fold increase in hippocampal ACh overflow which subsequently progressively declined over a 4-h period to pretreatment baseline levels. The combined injection of glucose with scopolamine resulted in a highly significant enhancement (19.4%; P less than 0.01) in ACh content of the first two samples as compared to saline-injected controls. These results provide the first direct experimental evidence that raised glucose levels, via increased availability of acetyl-coenzyme A (acetyl-coA), transiently facilitates ACh synthesis and release during conditions of increased neuronal activity. This enhancement of ACh availability during states of cholinergic neuronal activation may underlie the previously observed facilitatory effects of glucose on memory performance and its protection from scopolamine-induced amnesia.
    Behavioural Brain Research 09/1992; 49(2):181-8. DOI:10.1016/S0166-4328(05)80163-9 · 3.39 Impact Factor
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    ABSTRACT: We tested the effect of a single unilateral injection of a specific D1 agonist into the nucleus accumbens on the behavioral response to a subsequent unilateral intra-accumbens injection of a selective D2 agonist ten days later. The effect of the inverse order of presentation (D2 agonist followed ten days later by a D1 agonist) was also tested. No significant differences between the locomotor effects of the intra-accumbens injection of either SKF-38393 (3.5 micrograms) or LY-171555 (10 micrograms) were observed during the first test. Ten days later, during the second test, intra-accumbens injection of either the LY-171555 and SKF-38393 increased the percentage of contralateral rotations relative to the first test while LY-171555 also increased the total number of rotations. Control injections showed that these effects of LY-171555 and SKF-38393 were not due to a conditioning process. Rather, the results suggested that the locomotor changes observed during the second test were the result of behavioral sensitization due to the initial acute injection of the agonists.
    Life Sciences 02/1991; 49(9):PL43-8. DOI:10.1016/0024-3205(91)90118-U · 2.30 Impact Factor
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    ABSTRACT: The spatial working memory performances of young (2 months) and aged (24-26 months) mice of the C57BL/6 strain were compared using a delayed nonmatching to place (DNMTP) protocol in an automated 8-arm radial maze. The aged mice were observed to exhibit a selective and interference-related memory deficit. Parallel neurochemical analysis of the activity of septo-hippocampal and nbm-cortical cholinergic neurones in vivo was conducted using measures of sodium-dependent high-affinity choline uptake. Results showed that whereas the level of cholinergic activity in both brain regions varied less than 10% between young and aged mice in quiet conditions (basal) the activation usually observed at 30-sec posttest (+20-25%) in young mice was greatly attenuated in the frontal cortex and almost totally absent in the hippocampus of aged mice. In view of these results a complementary experiment was carried out in order to test the intrinsic ability of septo-hippocampal cholinergic neurones to activate using acute injection of scopolamine (1 mg/kg IP 20 min) to both young and aged mice in quiet conditions. The drug injection resulted in a very large (+70%) increase in hippocampal high-affinity choline uptake and with amplitudes which did not vary significantly between young and aged subjects. These observations attest to a relatively well-preserved state of central cholinergic neurones and an intact capacity to activate normally when challenged pharmacologically in aged mice. The results strongly suggest that the loss of cholinergic activation and associated memory deficit in aged mice might rather be related to a hypofunction of phasically active transsynaptic processes which normally mediate the activation of these cholinergic pathways during memory testing.
    Neurobiology of Aging 09/1990; 11(5):515-21. DOI:10.1016/0197-4580(90)90112-D · 4.85 Impact Factor
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    ABSTRACT: The effect of a 3 g/kg glucose injection on the velocity of the sodium-dependent high-affinity choline uptake mechanism in the hippocampus was both measured in quiet control mice and in mice immediately after training in an operant bar pressing task. Glucose did not significantly change high-affinity choline uptake in resting animals. High-affinity choline uptake in the hippocampus was increased by training in the operant bar pressing task. Glucose significantly reduced the amplitude of the increase in high-affinity choline uptake observed in the trained animals. Similarly, a 3 g/kg glucose injection also attenuated the increase in high-affinity choline uptake observed in animals injected with 1 mg/kg scopolamine. Finally, a 3 g/kg glucose injection significantly attenuated the amnesia produced by a post-training 1 mg/kg scopolamine injection in mice trained for an operant bar pressing task. These results provide additional evidence for an action of glucose on hippocampal cholinergic activity under conditions of high acetylcholine demand. This action may be mediated via an increase in acetyl coenzyme A availability, one of the precursors of acetylcholine. This facilitative effect of glucose on hippocampal acetylcholine synthesis may constitute the physiological basis for its facilitative action on memory and its attenuation of scopolamine amnesia.
    Behavioural Brain Research 08/1990; 39(2):135-43. DOI:10.1016/0166-4328(90)90100-S · 3.39 Impact Factor
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    ABSTRACT: In order to test the hypothesis that alpha-noradrenergic receptors in the septum 1) play an important functional role in the mediation of trans-synaptic control of the neurones of the cholinergic septo-hippocampal pathway and 2) produce resultant modulation of working memory performance, we have investigated the effects in vivo of the acute intraseptal injection of an alpha-antagonist, phenoxybenzamine, in mice. Neurochemical analysis was performed using measures of the kinetics of sodium-dependent high-affinity choline uptake in samples of hippocampus from injected mice and their relevant controls in both quiet conditions and immediately following selective working memory testing in an 8-arm radial maze. Results show that whereas the injection of phenoxybenzamine produces no significant alteration of the activity of the cholinergic septo-hippocampal neurones in quiet conditions, the pretrial (20 min) administration of this drug almost totally abolished the usually observed increase in hippocampal cholinergic activity induced by testing. This inhibition of cholinergic activation was associated with a parallel working memory deficit. The results provide further direct support for the hypothesis that septal noradrenergic afferents via alpha-receptors mediate a phasic and net excitatory trans-synaptic influence on the cholinergic septo-hippocampal pathway during working memory testing and thereby significantly contribute to the modulation of the level of working memory performance.
    Pharmacology Biochemistry and Behavior 12/1989; 34(3):553-8. DOI:10.1016/0091-3057(89)90557-1 · 2.82 Impact Factor

Publication Stats

1k Citations
136.71 Total Impact Points

Institutions

  • 1985–2007
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1989–2003
    • Université Bordeaux 1
      • UMR CNIC - Centre de Neurosciences Intégratives Cognitives
      Talence, Aquitaine, France
  • 1988
    • University of Bordeaux
      Burdeos, Aquitaine, France