Biomedical subjects

R J McDonald

Publications and source records attributed to R J McDonald.

At least 19 recordsLinked to original sources

PubMed2006

The role of medial prefrontal cortex in context-specific inhibition during reversal learning of a visual discrimination.

Rats with medial prefrontal cortex or sham lesions were trained on a visual discrimination task designed for the eight-arm radial maze. After reaching asymptotic performance on this task, both groups were divided into sub-groups that would experience reversal learning in the same or different context from original training. The results showed that both groups reversed in the different context had accelerated learning compared to the groups reversed in the same context. Reversal learning in rats with medial prefrontal cortex damage was faster than sham animals in the same context. These and other results from a transfer test suggest that the medial prefrontal cortex participates in the behavioral effects of a context-specific inhibitory association acquired during visual discrimination learning.

Animals↗

PubMed2005

Lesions of the dorsolateral striatum impair the acquisition of a simplified stimulus-response dependent conditional discrimination task.

The dorsal striatum has long been thought to be important for some types of learning and memory, especially stimulus-response learning. Recently, we demonstrated that selective lesions of the dorsolateral striatum, but not dorsomedial striatum in rats, retarded the acquisition of two instrumental discrimination tasks thought to require stimulus-response learning. However, since these studies investigated the effects of dorsal striatal lesions on task acquisition, which can be confounded by differences in level of reinforcement and motor impairment caused by the lesion, the interpretation of these findings was somewhat problematic. The present experiment was designed to address these issues by assessing the effects of lesions of the dorsolateral striatum on a simplified version of the conditional discrimination task, in which the importance of reinforcement and motor factors was minimized. Animals with lesions of the dorsolateral striatum showed marked impairments in learning this task, a finding that is in agreement with the notion that the dorsolateral striatum is necessary for stimulus-response learning.

Animals↗

PubMed2005

New limit on the neutrinoless betabeta decay of 130Te.

We report the present results of CUORICINO, a search for neutrinoless double-beta (0nu betabeta) decay of 130Te. The detector is an array of 62 TeO2 bolometers with a total active mass of 40.7 kg. The array is cooled by a dilution refrigerator shielded from environmental radioactivity and energetic neutrons, operated at approximately 8 mK in the Gran Sasso Underground Laboratory. No evidence for (0nu betabeta) decay was found and a new lower limit, T(1/2)(0nu) > or = 1.8 x 10(24) yr (90% C.L.) is set, corresponding to [m(nu)] < or = 0.2 to 1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis.

Journal Article↗

PubMed2005

Lesions of the dorsolateral or dorsomedial striatum impair performance of a previously acquired simple discrimination task.

Previous evidence has suggested a specific role for the dorsal striatum, especially the dorsolateral region of the dorsal striatum, in stimulus-response learning. In a previous study, we found an impairment in animals with dorsolateral striatal lesions on a simple discrimination task (CS+/CS-), thought to require the involvement of both stimulus-reward and stimulus-response learning. It is possible that the generally poor performance of dorsolateral lesioned animals on this experiment precluded adequate exposure to stimulus-reward pairings necessary for solving this task, and, thus, had little to do with stimulus-response learning. To test this hypothesis, the performance of animals with dorsolateral and dorsomedial striatal lesions was assessed on a previously acquired simple discrimination task. To independently assess the effects of each lesion on the performance of stimulus-reward learning, dorsolateral and dorsomedial lesioned animals were assessed on a previously acquired conditioned place preference task (CPP). In agreement with our earlier experiment, and the stimulus-response interpretation of dorsolateral striatal function, animals with dorsolateral striatal lesions were found to be impaired during post-lesion performance of the simple discrimination task, but not CPP learning. Additionally, dorsomedial lesioned animals were found to be impaired in performance of the simple discrimination task, but not on the CPP task. Possible explanations for the differences between the role of the dorsomedial striatum in acquisition and expression of the simple discrimination task are proposed.

Animals↗

PubMed2005

A role for adult neurogenesis in spatial long-term memory.

Adult hippocampal neurogenesis has been linked to learning but details of the relationship between neuronal production and memory formation remain unknown. Using low dose irradiation to inhibit adult hippocampal neurogenesis we show that new neurons aged 4-28 days old at the time of training are required for long-term memory in a spatial version of the water maze. This effect of irradiation was specific since long-term memory for a visibly cued platform remained intact. Furthermore, irradiation just before or after water maze training had no effect on learning or long-term memory. Relationships between learning and new neuron survival, as well as proliferation, were investigated but found non-significant. These results suggest a new role for adult neurogenesis in the formation and/or consolidation of long-term, hippocampus-dependent, spatial memories.

Animals↗

PubMed2004

Dorsal striatum and stimulus-response learning: lesions of the dorsolateral, but not dorsomedial, striatum impair acquisition of a simple discrimination task.

In the present experiment, the effects of neurotoxic lesions (quinolinic acid) of the dorsolateral or dorsomedial striatum were investigated on a simple instrumental discrimination task (CS+/CS-). Rats with lesions of the dorsolateral striatum were found to be impaired in the acquisition of this task, as compared to rats with either dorsomedial striatal or sham lesions. Furthermore, dorsolateral striatal lesioned animals had significantly lower levels of responding across the course of discrimination training, as assessed both by overall rate of response during CS+ presentations and number of CS+ trials without a response, despite having shown levels of responding during variable interval training that did not differ from that of sham lesioned animals. In contrast, animals with lesions of the dorsomedial striatum did not show an impairment in acquisition of the present task, but had slightly higher rates of responding during CS- presentations. It is argued that the poor acquisition and low response rates observed in animals with dorsolateral striatal lesions reflect a failure in stimulus-response learning, while the performance of animals with dorsomedial striatal lesions may have been the result of an increase in overall activity rate.

Animals↗

PubMed2004

Dorsal striatum and stimulus-response learning: lesions of the dorsolateral, but not dorsomedial, striatum impair acquisition of a stimulus-response-based instrumental discrimination task, while sparing conditioned place preference learning.

While some evidence suggests that the dorsal striatum is important for stimulus-response learning, disagreement exists about the relative contribution of the dorsolateral and dorsomedial striatum to this form of learning. In the present experiment, the effects of lesions of the dorsolateral and dorsomedial striatum were investigated on two tasks that differentially require the development of stimulus-response learning. The first task utilized an operant conditional discrimination task, which is likely to rely heavily upon stimulus-response learning. The second task looked conditioned place preference learning, a task that is unlikely to require the development of stimulus-response associations. Animals with lesions of the dorsolateral striatum were impaired on the operant conditional discrimination task, but retained the ability to learn the conditioned place preference task. In contrast, animals with lesions of the dorsomedial striatum were not found to be impaired on either task used in the present experiment. These results suggest that the dorsolateral striatum is necessary for the successful acquisition of tasks that place a demand upon stimulus-response learning, while the dorsomedial striatum is not involved in this type of learning.

Amygdala↗

PubMed2004

A dissociation of dorso-lateral striatum and amygdala function on the same stimulus-response habit task.

This experiment tested the idea that the amygdala-based learning and memory system covertly acquires a stimulus-reward (stimulus-outcome) association during acquisition of a stimulus-response (S-R) habit task developed for the eight-arm radial maze. Groups of rats were given dorso-lateral striatal or amygdala lesions and then trained on the S-R habit task on the eight-arm radial maze. Rats with neurotoxic damage to the dorso-lateral striatum were severely impaired on the acquisition of the S-R habit task but showed a conditioned-cue preference for the stimulus reinforced during S-R habit training. Rats with neurotoxic damage to the amygdala were able to acquire the S-R habit task but did not show a conditioned-cue preference for the stimulus reinforced during S-R habit training. This pattern of results represents a dissociation of learning and memory functions of the dorsal striatum and amygdala on the same task.

Amygdala↗

PubMed2001

Finding a goal on dry land and in the water: differential effects of disorientation on spatial learning.

Two previous studies, Martin et al. (J. Exp. Psychol. Anim. Behav. Process. 23 (1997) 183) and Dudchenko et al. (J. Exp. Psychol. Anim. Behav. Process. 23 (1997) 194), report that, compared to non-disoriented controls, rats disoriented before testing were disrupted in their ability to learn the location of a goal on a dry radial-arm maze task, but that both groups learned at the same rate in the Morris water maze. However, the radial-arm maze task was much more difficult than the water maze. In the current set of experiments, we examined the performance of control and disoriented rats on more comparable dry land and water maze tasks. Compared to non-disoriented rats, rats that were disoriented before testing were significantly impaired in locating a goal in a circular dry arena, but not a water tank. The results constrain theoretical explanations for the differential effects of disorientation on different spatial tasks.

Animals↗

PubMed2001

A cautionary note on interpreting the effects of partial reinforcement on place learning performance in the water maze.

The effects of partial reinforcement on dry land and swimming pool place learning tasks have recently been compared and it has been suggested that they differ fundamentally [8]. That is, partial reinforcement impairs performance in the water maze, but not on dry land. However, other evidence suggests that partial reinforcement may have the opposite effect in the water maze, strengthening the accuracy and persistence of spatial responses. We discuss how the discrepancy may depend on 'levels' of negative reinforcement (e.g. escaping to a submerged platform before complete removal from the pool) and how experimental procedures may set up competitive contingencies that reinforce alternative behaviors. Finally, we consider data from past lesion studies and suggest ways to improve the design of future water maze experiments.

Animals↗

PubMed2001

Dorsal/ventral hippocampus, fornix, and conditioned place preference.

Conditioned place preference (CPP) is a learning paradigm requiring formation of associations between reward and particular locations. White and McDonald (Behav Brain Res 1993;55:269-281) demonstrated that amygdala (AMG) lesions impair, while fornix (Fx) lesions enhance learning of this task. In the present experiments, we replicated the effects of AMG and Fx lesions, but we also found that complete hippocampal (HPC) lesions interfere with normal performance. Thus, the effects of Fx and HPC lesions on CPP are opposite. This is in contrast with spatial learning in the water maze. Because it has been demonstrated that damage of dorsal HPC interferes to a greater extent with spatial learning than damage of ventral HPC, we also tested animals with either dorsal or ventral HPC disruptions on CPP. Lesions limited to dorsal HPC were followed by impairment on this task. In contrast, lesions limited to ventral HPC resulted in enhanced learning. We argue that Fx and HPC lesions do not have interchangeable effects in all learning paradigms. To explain the complex pattern of results presently obtained, we propose a novel hypothesis regarding behavioral functions of HPC neural circuits. Implications regarding the interaction between memory systems are also considered.

Animals↗

PubMed2001

Circadian phase-shifted rats show normal acquisition but impaired long-term retention of place information in the water task.

It is thought that circadian rhythms may influence learning and memory processes. However, research supporting this view does not dissociate a mnemonic impairment from other performance deficits. Furthermore, published reports do not specify the type of memory system influenced by the circadian system. The present study assessed the effects of phase shifting on acquisition and expression of place navigation in the water maze, a task sensitive to hippocampal dysfunction. The results showed that phase-shifting circadian rhythms in rats impaired the expression of place information on a retention test but not initial acquisition or encoding of place information. These results suggest that disruption of circadian rhythms may impair consolidation of previously encoded hippocampal place information.

Animals↗

PubMed2001

Amygdala, hippocampus, and unconditioned fear.

Embedded within contemporary views of emotional learning is a well-founded agreement that the amygdala plays a pivotal role in the formation and consolidation of aversive memories formed during fear conditioning. However, it is important to determine whether observed deficits are reflective of a memory impairment or whether they are simply attributable to a deficit in the performance of unconditioned fear responses such as freezing. Within the neurobiology of learning and memory literature, there is an ongoing debate concerning the potential role of the amygdala in the performance of unconditioned fear responses. A view put forth by Vazdarjanova and McGaugh (1998) suggests that the amygdala is not required for the formation and consolidation of the aversive memories formed during fear conditioning, but is essential in the performance of unconditioned fear responses. Data provided by Maren (1999) counter this view by positing that the amygdala is not required for the performance of fear responses, but its role is of a mnemonic nature in the conditioning of fear to neutral cues. To clarify the amygdala's participation in these two processes, a useful approach would involve a situation where animals with amygdala damage were examined for their unconditioned fear responses in reaction to footshock as well as the conditioning of these reactions to previously neutral cues paired with the aversive event. We have previously reported that rats with amygdala or hippocampal damage are impaired in discriminative fear conditioning to context. In the present experiment, we report the initial unconditioned fear responses to footshock by these same animals as well as the conditioned responses during testing. In both groups, the fear responses assessed (freezing, urination, defecation, and locomotion) were not impaired and did not differ from those expressed by the sham animals. The impairment of discriminative fear conditioning to context, in combination with the present experiment, represents a dissociation where damage to specific memory structures (amygdala or hippocampus) debilitates the mnemonic processes involved in fear conditioning, but not the performance of the fear responses per se.

Amygdala↗

PubMed2001

Context-specific interference on reversal learning of a stimulus-response habit.

Learning occurs in a particular place and time. In most learning situations, information about the training context is encoded along with the task demands and solution. However, the extent to which context contributes to the acquisition and expression of a particular learned response is unclear. In the present paper we examined two fundamental issues underlying the importance of context information and its role in expression of discrimination learning and reversal learning. Rats were trained on a stimulus-response (S-R) habit task designed for the eight-arm radial maze and after reaching a set criterion different context manipulations were performed. Results from Section 2.2.1 revealed that although rats detected a change in context, the learning was not context specific. Results from Section 2.2.2 showed that S-R reversal learning was enhanced when animals were reversed in a context that was different from the one used during original training. Animals that were reversed in a different context showed a renewal effect to the initial S-R when brought back to the original training context.

Animals↗

PubMed2001

Pharmacologic management of the hospitalized pediatric asthma patient.

Explore the source record for details and available documents.

Adolescent↗

PubMed2000

Circadian rhythms, aging and memory.

In human beings and animal models, cognitive performance is often impaired in natural and experimental situations where circadian rhythms are disrupted. This includes a general decline in cognitive ability and fragmentation of behavioural rhythms in the aging population of numerous species. There is some evidence that rhythm disruption may lead directly to cognitive impairment; however, this causal link has not been made for effects due to aging. We have tested this link by examining rhythms and performance on contextual conditioning with the conditioned place preference task, in elderly, age-matched hamsters. Young healthy hamsters developed a preference for a context that is paired with the opportunity to engage in wheel-running (experiment 1). Aged animals with consolidated locomotor rhythms developed similar degrees of preference, whereas the age-matched hamsters with fragmented rhythms did not (experiment 2). The degree of preference was also correlated with activity amplitude. These results support the notion that age-related rhythm fragmentation contributes to the age-related memory decline.

Aging↗

PubMed2000

Rats with hippocampal damage are impaired on place learning in the water task when overtrained under constrained conditions.

To date, numerous investigations have been conducted on the mammalian hippocampus to determine its precise function. This research has implicated a fundamental role for the hippocampus in the formation of a spatial map that an animal can use to appropriately guide behavior in complex relational tasks. Despite substantial evidence to support this view, there have been challenges to this theory of hippocampal function. One alternative view suggests that the hippocampus is involved with the integration and updating of voluntary movement. Therefore, any impairments expressed by rats with hippocampal damage are not due to the inability to form or use a spatial map, but rather arise because they are unable to accurately control and monitor on-line movement. Accordingly, investigators, supporting the latter, claim that animals with hippocampal lesions are able to solve a spatial version of the water task if they are given explicit training on how to get to the hidden platform. In the present study we trained rodents with or without hippocampal damage on a cue/place water task for 40 days. In using behaviorally constraining procedures and by overtraining these animals, we provided them with knowledge of how to get to the hidden platform, and ensured enough time to learn the task. Our findings revealed that although rats with hippocampal lesions showed some place responses, they were significantly impaired on all measures of place learning compared to sham animals under these intensive procedures. Overall, the results of the present study do not support the idea that the hippocampus is not specifically involved in acquisition of place information in the water task.

Animals↗

PubMed2000

Circadian rhythms, aging and memory.

Aging↗