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T Durkin

Publications and source records attributed to T Durkin.

At least 19 recordsLinked to original sources
PubMed2006

Observation of muon neutrino disappearance with the MINOS detectors in the NuMI neutrino beam.

This Letter reports results from the MINOS experiment based on its initial exposure to neutrinos from the Fermilab NuMI beam. The rates and energy spectra of charged current nu(mu) interactions are compared in two detectors located along the beam axis at distances of 1 and 735 km. With 1.27 x 10(20) 120 GeV protons incident on the NuMI target, 215 events with energies below 30 GeV are observed at the Far Detector, compared to an expectation of 336+/-14 events. The data are consistent with nu(mu) disappearance via oscillations with |Delta(m)2/32|=2.74 +0.44/-0.26 x10(-3)eV(2) and sin(2)(2theta(23))>0.87 (68% C.L.).

Journal Article↗
PubMed1999

Performance of open-fronted microbiological safety cabinets: the value of operator protection tests during routine servicing.

The performance of class I and II microbiological safety cabinets over 7 years, employed in a force-ventilated containment level 3 (CL-3) laboratory, is described. Operator Protection (OP) provided by the cabinets, assessed by still and latterly limited 'in-use' KI-Discus tests, showed no overall deterioration during the review period. Comparisons show that a selected class II unit, but not a second, and a new class II MSC in a recently commissioned, similar CL-3 facility, provide the same order of OP as a class I cabinet. From the experiences described, it is strongly recommended that OP tests (OPTs) should be part of the routine servicing regime to ensure that cabinets meet required performance levels, and additionally to allow detection and rectification of poor containment, particularly where induced by environmental factors. The value of OPTs is discussed with reference to certain national standards.

Containment of Biohazards↗
PubMed1999

The cultural context model: therapy for couples with domestic violence.

This article offers a brief analysis of heterosexual dominance within various cultures toward a larger understanding of domestic violence. It then describes the Cultural Context Model, developed over 15 years of experience treating domestic violence in its broader context, utilizing separate "culture circles" for men and women before and during couple therapy. It then identifies guidelines for assessment and intervention with a discussion of the special issues raised when substance abuse is involved.

Culture↗
PubMed1997

Sex-linked behavioural differences in mice expressing a human insulin transgene in the medial habenula.

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.

Animals↗
PubMed1990

Memory-improving action of glucose: indirect evidence for a facilitation of hippocampal acetylcholine synthesis.

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.

Acetylcholine↗
PubMed1989

In vivo modulation of septo-hippocampal cholinergic activity in mice: relationships with spatial reference and working memory performance.

Dopaminergic afferents to the septum mediate a tonic and trans-synaptic inhibitory control on the cholinergic neurones of the septo-hippocampal pathway. Lesion of these afferents using 6-hydroxydopamine (6-OHDA) results in a chronic and specific increase of hippocampal cholinergic activity in mice. The consequence of this in vivo modulation of hippocampal cholinergic activity on the acquisition of both a spatial discrimination and a working memory (delayed non-matching to place) task in an 8-arm radial maze by C57BL/6 mice were investigated. Combined neurochemical and behavioural analyses revealed significant correlations between hippocampal sodium-dependent high-affinity choline uptake activation induced by testing and performance measures. In the first experiment 6-OHDA-treated mice compared to control and vehicle-injected mice showed a transient (day 2) but significant facilitation of their spatial discrimination performance which appears to be better related to the working but not to the reference memory component of the task. This hypothesis is strengthened by the results of the second experiment which shows an amelioration of working memory performance when the septo-hippocampal cholinergic pathway is specifically activated in vivo.

Afferent Pathways↗
PubMed1989

Septal alpha-noradrenergic antagonism in vivo blocks the testing-induced activation of septo-hippocampal cholinergic neurones and produces a concomitant deficit in working memory performance of mice.

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.

Action Potentials↗
PubMed1989

The durations of hippocampal and cortical cholinergic activation induced by spatial discrimination testing of mice in an eight-arm radial maze decrease as a function of acquisition.

Sodium-dependent high-affinity choline uptake velocities in P2 fractions of the hippocampus and cortex of mice were analyzed at different times following both the first (Day 1) and last (Day 9) daily sessions of a spatial discrimination testing procedure in an eight-arm radial maze. Results showed that the immediate (30 s) post-training increase in mean hippocampal and cortical cholinergic activity observed on Day 1 did not significantly vary over days despite a marked and progressive improvement of discrimination performance. In contrast, the duration of these activations was considerably shortened in both structures between Days 1 (more than 1 hr) and 9 (about 15 min). The possible involvement of these changes in memory consolidation processes is discussed.

Animals↗
PubMed1989

Experimental dissociation of memory systems in mice: behavioral and neurochemical aspects.

Evidence for different types of memory in mice may lead to development of animal models for human memory disorders and provides informations on neurobiological systems underlying these processes. Series of experiments in mice, using a 8-arm radial maze with or without cholinergic drugs or chronic alcohol consumption supply arguments for multiple memory stores and for cholinergic influence greatest for short-term system. Studies of differential cholinergic activation following training militate for dissociation in time of hippocampal and cortical cholinergic pathways. Age-related memory involvement seems to be associated with an attenuation of central cholinergic activation. Several problems inherent to sensitivity and selectivity of the tasks remain in discussion.

Animals↗
PubMed1988

Electrical self-stimulation in the medial and lateral septum as compared to the lateral hypothalamus: differential intervention of reward and learning processes?

The characteristics of the electrical self-stimulation behavior elicited from the lateral hypothalamus (LH) and from both medial (MS) and lateral (LS) parts of the septal nucleus have been compared in male mice of the BALB/c strain. Using two different experimental situations (the lever-press box and a spatial discrimination test in a Y-maze) the self-stimulation rate-current intensity relations and the performances during both acquisition and reversal of a spatial discrimination were tested successively. In the lever-press box, it was observed that highest self-stimulation rates were obtained from LH placements while both MS and LS rates were lower. However, MS animals showed higher self-stimulation rates and lower self-stimulation thresholds than LS animals. Acquisition of the spatial discrimination in the Y-maze was achieved by all 3 groups with similar time courses. However, when tested for the reversal of the discrimination, the LS implanted mice were much more perturbed than the two other groups and exhibited marked perseveration. The incidence of convulsive episodes was more frequent in LS mice than in either MS or LH implanted animals during both phases of the discrimination task. These differences in the self-stimulation behavior elicited from medial and lateral parts of the septal complex are discussed in relation to the operation of positive reinforcement mechanisms and to internal inhibition processes operating during acquisition and reversal of the spatial discrimination.

Animals↗
PubMed1988

Differential hippocampal and cortical cholinergic activation during the acquisition, retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze by mice.

Possible differentiation of the intervention of cholinergic septohippocampal and magnocellular forebrain (NBM) projections to cortex during learning and memory processes has been investigated directly using mice. High-affinity choline uptake velocities in the hippocampus and cortex were analyzed, in parallel, at various periods during the acquisition, over 8 days, as were the subsequent retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze. Initial acquisition induced an immediate (30 s) and long-lasting (approx. 3 h) increase in mean hippocampal (+33%) and cortical (+23%) cholinergic activities. The time course of this activation was structure-dependent and correlations of hippocampal-cortical cholinergic activities showed large and consistent alterations as a function of time after training. Cholinergic activation in both brain regions was observed immediately following each daily training session with amplitudes which did not vary significantly in spite of a progressive daily increment in performance. Following acquisition mice were tested for retention, reversal and extinction: 30 s following the retention session, cholinergic activation was observed in both cortex and hippocampus, with magnitudes similar to those observed at the end of acquisition. However, in the reversal and extinction groups, a treatment-dependent attenuation of cholinergic activation was observed which was accompanied by a significant loss of correlation of cholinergic activity between these two brain regions. The results are discussed in relation to the concepts of reference and working memory and also to novelty, stress, arousal and frustrative non-reward. The data constitute direct experimental evidence for a differential involvement of cholinergic septohippocampal and NBM-cortical projections in learning and memory processes.

Animals↗
PubMed1987

The effect of diazepam on hippocampal EEG in relation to behavior.

Male mice of the BALB/cByJ and C57BL/6 strains were implanted with electrodes in the CA1 area of the hippocampus to record rhythmic slow-wave activity (RSA) or 'theta' EEG activity. The EEG spectral characteristics and the animal's motor behavior were studied while the animals walked on a moving belt (2.2 cm/s) both before and after i.p. injections of diazepam (Valium, 2 mg/kg) or vehicle. EEG spectral analyses were carried out on-line by computer. Diazepam produced a dissociation of locomotion and RSA. (1) Uninjected and vehicle-injected mice showed typical RSA (7-8 Hz) while walking. (2) Under diazepam, 7-8 Hz RSA virtually disappeared and was replaced in the temporally averaged records by RSA with a sharp, narrow-band peak at 4-5 Hz. (3) This lower-frequency RSA was associated with immobility if, and only if, the immobility immediately followed walking. This was true whether the animal itself stopped walking or the experimenter stopped the moving belt. This theta activity predominated for about 30 s and had disappeared after 2 min. Locomotion, on the other hand, was accompanied by irregular EEG activity. (4) Scopolamine (i.p. 1 mg/kg), a cholinergic blocker, greatly reduced the diazepam-induced 4-5 Hz RSA, but also partially restored 7-8 Hz RSA. The possibility that the effects of diazepam on hippocampal EEG involve changes in septohippocampal cholinergic activity is discussed.

Animals↗
PubMed1986

Inhibition of endothelial cell proliferation by type beta-transforming growth factor: interactions with acidic and basic fibroblast growth factors.

TGF beta is a potent (ED50 approximately 10(-11) M) inhibitor of the proliferative activities of both acidic and basic FGF on vascular and capillary endothelial cells in vitro. The inhibition of cell growth is dose-dependent and characteristic of a non-competitive interaction. The results demonstrate that TGF beta and FGF can interact at the cellular level to modulate growth and suggest that many of the biological activities of FGF observed in vitro and in vivo (ie angiogenesis, cell growth, cell differentiation) may be regulated by the presence of TGF beta and related proteins (ie inhibin) in the local cellular milieu. The possible identity of TGF beta with the inhibitors of endothelial cell growth detected in in vitro assays of crude extracts is discussed.

Animals↗
PubMed1986

The effects of acute intraseptal injection of haloperidol in vivo on hippocampal cholinergic function in the mouse.

Acute injection of haloperidol into the lateral septum in mice produced an immediate and long-lasting increase in hippocampal sodium-dependent high-affinity choline uptake. Parallel electrophysiological investigations revealed that the increased septo-hippocampal cholinergic activity augmented CA1 pyramidal cell excitability and also accelerated the extinction of a conditioned reinforcement. These results constitute further evidence that septal dopaminergic terminals, via their control of septo-hippocampal cholinergic activity play a significant role in the modulation of hippocampal function.

Animals↗
PubMed1985

Facilitation of spontaneous and learned spatial behaviours following 6-hydroxydopamine lesions of the lateral septum: a cholinergic hypothesis.

Mice received injections of 6-hydroxydopamine (6-OHDA) in the lateral septum; they were tested for spontaneous alternation, acquisition and reversal of a spatial discrimination in a T-maze. In each of these tasks, performance of 6-OHDA lesioned mice was improved relative to controls. Neurochemical analysis revealed that 6-OHDA lesioned mice exhibited a significant increase in the rate of sodium-dependent high affinity choline uptake in the hippocampus. These results are discussed in relation to current theories concerning the role of the septo-hippocampal complex and cholinergic system in the control of behaviour.

Animals↗
PubMed1985

Cholinergic neurotransmission in the central nervous system of the Snell dwarf mouse.

An unequal decrease in cholinergic activity has been evidenced in discrete brain areas in the growth hormone, thyroid-stimulating hormone and prolactin deficient Snell dwarf mouse. The effect of the mutation's pituitary deficit on central cholinergic mechanisms appears to be selective: Normally high cholinergic activity areas such as striatum, olfactory tubercles, and hippocampus show strong alterations in this neurotransmitter system. Structures which appear earlier in ontogenesis are less affected, if at all. The lack of pituitary hormones seems to have effects on choline acetyltransferase activity and/or synthesis as well as on the development of high affinity (H.A.) cholinergic uptake mechanisms, both strongly defective in hippocampus and striatum. Therefore, a lower density of cholinergic terminals can be inferred. Furthermore, our observations are consistent with a close functional coupling of the choline H.A. transport and of subsequent choline acetylation. Acetylcholinesterase activity does not seem to be affected. Moreover, a compensatory effect at the postsynaptic level may have occurred due to developmental or functional plasticity for cholinergic responsiveness. In conclusion, the dwarf mouse seems to be a useful model for a better understanding of the influences of growth hormone and thyroid hormones on the development of central cholinergic mechanisms. It also provides the possibility to attempt a functional restoration of the deficient cholinergic neurotransmission and the behavioral disturbances which may be linked to them, by hormone replacement.

Acetylcholinesterase↗
PubMed1984

[Improvement in spontaneous and acquired spatial behaviors following lesions of septal dopaminergic afferents in mice: possible relations with hippocampal cholinergic activity].

Recent evidence from pharmacological studies support the view that dopaminergic afferents to the septal complex which originate from the mesencephalic A10 area, exert a tonic inhibitory control over the activity of the septal-hippocampal cholinergic neurons. Accordingly one could predict that the release from such an inhibition by lesion of the septal dopaminergic terminals might improve performance in tasks known to be related to hippocampal cholinergic activity. In order to test this hypothesis mice of the C57BL/6 strain received a bilateral injection of 6-hydroxydopamine in the lateral septal nucleus; they were compared to subjects receiving saline and to unoperated control mice in tests performed in a T-maze: spontaneous alternation, acquisition and reversal of spatial discrimination. In all tasks, performance of experimental subjects was improved relative to controls. However, subsequent experiments showed that this improvement was not observed when visual (light/dark) discrimination was used. Finally, 6-hydroxydopamine injected mice exhibited a substantial increase in hippocampal sodium-dependent high affinity choline uptake (+ 16.7%). These results are discussed in relation to the three main theories concerning the role of the septo-hippocampal complex and cholinergic system in the control of behavior (i.e. Pavlovian internal inhibition, spatial mapping and working memory). Only the theory of spatial cognition seems to account for our present findings.

Afferent Pathways↗