Janice L. Muir
Cardiff University
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Featured researches published by Janice L. Muir.
The Journal of Neuroscience | 1994
Angela C. Roberts; M. A. De Salvia; Lawrence Stephen Wilkinson; P. Collins; Janice L. Muir; Barry J. Everitt; Trevor W. Robbins
The effects of 6-hydroxydopamine lesions of the prefrontal cortex in monkeys were investigated on two cognitive tests of prefrontal function, spatial delayed response, and attentional set shifting. The latter test provided a componential analysis of the Wisconsin Card Sort Test, a commonly used clinical test of frontal lobe function in man. Acquisition of a visual compound discrimination requiring a shift of attention from one dimension to another (extradimensional shift), for example, shapes to lines, was significantly improved. This enhancement was behaviorally specific in that there were no effects on acquisition of a discrimination that required the continued maintenance of an attentional set toward one particular dimension (intradimensional shift), nor any effects on a series of visual or spatial discrimination reversals that involved the repeated shifting of responding between two exemplars from the same dimension. In contrast, spatial delayed response performance was impaired, in agreement with previous results. Neurochemical measures showed a marked depletion of dopamine limited to the prefrontal cortex and a smaller loss of prefrontal noradrenaline. This was accompanied by a long-term adaptive change in the striatum such that extracellular dopamine in the caudate nucleus, as measured by in vivo microdialysis, was elevated in response to potassium stimulation as long as 18 months postsurgery. It is proposed that attentional set shifting is mediated by a balanced interaction between prefrontal and striatal dopamine, and that elevated dopamine contributes to the improvement in attentional set-shifting ability. This interpretation is consistent with the impairment in attentional set-shifting ability observed in patients with Parkinsons disease or with damage to the frontal lobes using the same test as used here for infrahuman primates.
Pharmacology, Biochemistry and Behavior | 1997
Janice L. Muir
A substantial body of literature has suggested that the memory and learning deficits associated with Alzheimers disease and aging are attributable to degeneration of the cholinergic magnocellular neurons of the nucleus basalis of Meynert (nbM). Subsequently, lesion-induced damage to the cholinergic projections from the nbM to the neocortex has been utilized extensively as an animal model of dementia. In addition, the effect of the normal aging process on deterioration of these neurons and on cognitive function has also been examined. Such studies have revealed, for example, that many of the learning and memory impairments traditionally attributed to the cholinergic corticopetal system are not due to degeneration of the cholinergic neurons of the nbM, but instead may be due to damage of more rostral elements of the cholinergic basal forebrain system. This review will examine the contribution of behavioural animal and human studies to out understanding of the role of the basal forebrain cholinergic neurons in age-related cognitive impairments.
Experimental Brain Research | 1992
Janice L. Muir; Stephen B. Dunnett; Trevor W. Robbins; Barry J. Everitt
SummaryDegeneration of the cholinergic magnocellular neurons in the basal forebrain and their cortical projections is a major feature of the neuropathology of Alzheimers disease. In the present study, two experiments examined the disruptive effects on visual attentional performance of two different manipulations that reduce central cholinergic function. In Expt. I, pharmacological manipulation of the cholinergic system was investigated using icv administration of hemicholinium (HC-3), a 9high affinity choline uptake blocker, administered either alone or in conjunction with the anticholinesterase, physostigmine. The results revealed impairments in the ability of the rats to localize brief visual targets in a serial reaction time task, as shown in particular by a reduction in choice accuracy and lengthening of the latency to respond correctly to the visual stimulus. Cholinergic specificity was supported by the reversal of these behavioural impairments by pre-treatment with the anticholinesterase, physostigmine. In Expt. II, quisqualateinduced lesions of the basal forebrain produced behavioural deficits at 3 weeks post-lesion surgery similar to those observed following icv infusion of HC-3. In an attempt to restore the extrinsic cortical cholinergic innervation by reinnervation of the deafferented cortex, embryonic basal forebrain cholinergic cells were transplanted into the cortex of lesioned animals. After three months recovery, impairments in performance on the baseline schedule of the task were no longer apparent in lesioned animals. However, behavioural deficits, observed predominantly as a lengthening of correct response latency, could be reinstated in the lesioned animals by interpolation of distracting bursts of white noise during each trial, and this deficit was ameliorated by the cholinergic grafts. Furthermore, a non-specific effect of both cholinergic and non-cholinergic grafts in controlling the increase in perseverative time-out responses which occurred as a result of the basal forebrain lesion was consistently observed. These results suggest that cholinergic dysfunction can produce deficits in visual attention which can be ameliorated by cholinergic treatments such as physostigmine or cholinergic-rich cortical grafts. These data provide support for a role for the basal forebrain-neocortical cholinergic projection in attentional function.
Psychopharmacology | 1995
Barry J. Everitt; Trevor W. Robbins; Janice L. Muir
To investigate further the cholinergic specificity of the effects of basal forebrain lesion-induced disruption of attentional performance, the present study examined the efficacy of various pharmacological agents in improving performance of a five-choice serial reaction time task in rats that had received lesions of the cholinergic basal forebrain. Specifically, the effects of the novel 5-HT3 receptor antagonist, ondansetron (0.3, 1, 10 ng/kg), and of nicotine (0.03, 0.06, 0.1, 0.3 mg/kg) and the anticholinesterase, physostigmine (0.05, 0.1 mg/kg), on attentional function were examined in animals which had received AMPA-induced lesions of the nucleus basalis magnocellularis (nbM). The behavioural impairments observed immediately following the lesion were a reduction were choice accuracy and an increase in correct response latency. Although these impairments showed recovery over the course of the following weeks, the deficit in choice accuracy could be reinstated by reducing the duration of the visual stimulus and thus increasing the attentional load placed on the animals. This reduction in choice accuracy could be dose dependently improved by systemic administration of either physostigmine or nicotine, suggesting that this impairment in attentional function may be attributed to disruption of cholinergic function. The pharmacological specificity of these improvements was supported by the inability ofd-amphetamine to improve task performance (0.2, 0.4, 0.8 mg/kg). Ondansetron was also unable to improve accuracy of performance in lesioned animals, but was effective in reducing the anticipatory or premature responding observed in both control and lesioned animals, even when elevated (in the case of controls) by treatment with systemicd-amphetamine. The results of the present study therefore suggest that cholinergic dysfunction can lead to attentional impairments which can be ameliorated by cholinergic treatments such as physostigmine and nicotine, but that ondansetron, despite its proposed ability to release cortical acetylcholine, was unable to restore choice accuracy at the doses employed. The results further suggest a double dissociation of effects on accuracy and the disinhibition of responding.
Behavioural Brain Research | 2000
Timothy J. Bussey; Janette Duck; Janice L. Muir; John Patrick Aggleton
The present study provides evidence that lesions of the fornix (FNX) and of the perirhinal/postrhinal cortex (PPRH), which both disconnect the hippocampus from other brain regions, can lead to distinct patterns of behavioural impairments on tests of spatial memory and spontaneous object recognition. For example, whereas FNX lesions impaired allocentric spatial delayed alternation in a T-maze but generally spared a test of spontaneous object recognition, PPRH lesions produced the opposite pattern of results. Indeed, on the T-maze task PPRH animals significantly outperformed controls when the retention delay was increased to 60 s. In addition, some evidence was found that contributions from both the fornix and perirhinal/postrhinal cortex may be required when object and spatial information must be integrated. In an object-in-place test, for example, PPRH animals failed according to two measures, and FNX animals failed according to one measure, to discriminate objects that had remained in fixed locations from those that had exchanged locations with other objects. Neither lesion, however, affected performance of a visuospatial conditional task, a Pavlovian autoshaping task, or a one-pair pattern discrimination task. It is suggested that the perirhinal/postrhinal cortex, rather than being specialised for a particular type of associative learning, is important for processing complex visual stimuli.
Behavioural Brain Research | 1993
Janice L. Muir; Keith J. Page; D.J.S. Sirinathsinghji; Trevor W. Robbins; Barry J. Everitt
A substantial body of literature has suggested that the memory and learning deficits associated with Alzheimers disease are attributable to degeneration of the cholinergic magnocellular neurons of the nucleus basalis of Meynert (nbM). Subsequently, lesion-induced damage to the cholinergic projections from the nbM to the neocortex has been utilized extensively as an animal model of dementia. Ibotenic acid lesions of the basal forebrain have been found, for example, to produce deficits in a wide variety of tasks involving learning and memory. However, recently, with the availability of more potent cholinergic excitotoxins such as AMPA, it has become apparent that nbM lesions do not provide a simple animal model of the cognitive deficits in ageing and Alzheimers disease. Further analysis suggests that many of the learning and memory impairments traditionally attributed to the cholinergic corticopetal system are due not to destruction of cholinergic neurons in the nbM, but instead result from the disruption of cortico-striatal outputs passing through the dorsal and ventral globus pallidus. Furthermore, experiments utilizing quisqualic acid and AMPA have revealed that the most convincing deficit observed as a result of such lesions is in visual attention. This role for the basal forebrain-cortical cholinergic system in attentional function is further supported by results obtained from complementary pharmacological studies. This does not exclude a role for acetylcholine in learning and memory processes. Rather, such cognitive processes appear to depend not upon the integrity of the nbM itself, but upon more rostral elements of the cholinergic basal forebrain system.
The Journal of Neuroscience | 2001
E. Clea Warburton; Alison Lambie Baird; Angela Morgan; Janice L. Muir; John Patrick Aggleton
A disconnection procedure was used to test whether the hippocampus and anterior thalamic nuclei form functional components of the same spatial memory system. Unilateral excitotoxic lesions were placed in the anterior thalamic (AT) nuclei and hippocampus (HPC) in either the same (AT-HPC Ipsi group) or contralateral (AT-HPC Contra group) hemispheres of rats. The behavioral effects of these combined lesions were compared in several spatial memory tasks sensitive to bilateral hippocampal lesions. In all of the tasks tested, T-maze alternation, radial arm maze, and Morris water maze, those animals with lesions placed in the contralateral hemispheres were more impaired than those animals with lesions in the same hemisphere. These results provide direct support for the notion that the performance of tasks that require spatial memory rely on the operation of the anterior thalamus and hippocampus within an integrated neural network.
European Journal of Neuroscience | 1999
Mark Andrew Good; Mark Day; Janice L. Muir
The present study investigated the effects of naturally fluctuating endogenous levels of oestrogen on the induction and maintenance of long‐term potentiation (LTP) and long‐term depression (LTD) in the CA1 region of the hippocampus. Using an anaesthetized in vivo preparation, the results showed that the induction of LTP was augmented during the pro‐oestrous stage of the oestrous cycle. In contrast to LTP, however, the induction of paired‐pulse LTD was severely attenuated during pro‐oestrous, but was clearly manifested by rats during met/dioestrous and oestrous stages of the cycle. These findings are discussed with reference to: (i) the modulatory effects of oestrogen on N‐methyl‐d‐aspartate (NMDA) receptor function and γ‐aminobutyric acid (GABA) neurotransmission in the hippocampus; and (ii) the functional implications that such cyclical changes in synaptic plasticity have for learning and memory processes supported by the hippocampus.
European Journal of Neuroscience | 2003
Laura H. Corbit; Janice L. Muir; Bernard W. Balleine
Two experiments examined the effects of bilateral excitotoxic lesions of either the mediodorsal (MD) or anterior (ANT) thalamic nuclei on instrumental acquisition and performance, sensitivity to changes in the value of the instrumental outcome, and sensitivity to changes in the instrumental contingency. Rats were food deprived and trained to press two levers, each earning a unique food outcome (pellets or sucrose). All rats acquired the instrumental response although ANT lesions appear slightly to increase and MD lesions slightly to suppress instrumental performance. After training, specific satiety‐induced devaluation of one of the two instrumental outcomes produced a selective reduction in responding on the lever that in training had earned the now devalued outcome but only in the SHAM and ANT groups. In contrast, MD animals failed to show evidence of a selective devaluation effect when tested in extinction. Additionally, SHAM and ANT animals selectively decreased responding when one action‐outcome contingency was degraded, whereas MD animals reduced responding nonselectively on the two levers. Subsequent tests established that an inability to discriminate between either the two actions or the two outcomes cannot account for the lack of selective responding observed in the MD animals. Together these data suggest that MD lesions produce a profound deficit in the ability of rats to utilize specific action–outcome associations and appear to render rats relatively insensitive to the causal consequences of their instrumental actions. In contrast, far from producing a deficit, ANT lesioned rats were as sensitive to the effects of these behavioural manipulations as the sham lesioned controls.
Neuroscience | 1992
Angela C. Roberts; Trevor W. Robbins; Barry J. Everitt; Janice L. Muir
The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain were studied on performance of a series of visual discrimination tests that examined a range of cognitive functions in the marmoset. These included the ability to attend to the various dimensional properties of stimuli and to use just one of these properties in order to solve a discrimination (intra-dimensional shift); to switch attention from one dimension to another (extra-dimensional shift); to learn the reinforcement value of specific exemplars within a dimension (new learning); and to relearn their reinforcement value following reversal of the reward contingencies (serial reversals). Lesions of the basal forebrain did not impair the ability either to attend selectively to the dimensional properties of the stimuli or to switch attention from one dimension to the other. However, the lesion did affect various aspects of associative learning including a transient impairment of new learning and a marked disruption of serial reversal learning. The reversal deficit could be characterised as a tendency to perseverate on the previously correct stimulus and as a failure to to show the formation of a reversal learning set. In addition, the lesion prevented disruption of performance of a well-learned discrimination when novel exemplars from the irrelevant dimension were introduced (probe test). It is suggested that the functional effects of the basal forebrain lesion reflect impaired learning of stimulus-reward associations and behavioural rigidity. The finding, however, that there was no effect of the lesion on attentional set-shifting suggests that any loss of inhibitory control was specific to the level of stimulus-response or stimulus-reward associations, inhibitory control at the level of attentional selection remaining intact. The similarity of the effects of damage to the basal forebrain to those seen following damage to the orbitofrontal cortex and the amygdala are discussed in the context of the close anatomical and functional relationships that exist among these three structures.