Biomedical subjects

David M Bannerman

Publications and source records attributed to David M Bannerman.

10 recordsLinked to original sources

PubMed2006

Separate neural pathways process different decision costs.

Behavioral ecologists and economists emphasize that potential costs, as well as rewards, influence decision making. Although neuroscientists assume that frontal areas are central to decision making, the evidence is contradictory and the critical region remains unclear. Here it is shown that frontal lobe contributions to cost-benefit decision making can be understood by positing the existence of two independent systems that make decisions about delay and effort costs. Anterior cingulate cortex lesions affected how much effort rats decided to invest for rewards. Orbitofrontal cortical lesions affected how long rats decided to wait for rewards. The pattern of disruption suggested the deficit could be related to impaired associative learning. Impairments of the two systems may underlie apathetic and impulsive choice patterns in neurological and psychiatric illnesses. Although the existence of two systems is not predicted by economic accounts of decision making, our results suggest that delay and effort may exert distinct influences on decision making.

Animals↗

PubMed2005

Amphetamine promotes task-dependent recovery following focal cortical ischaemic lesions in the rat.

This study investigated the effect of amphetamine (AMP) on skilled forelimb use following focal cortical ischaemic lesions in the rat. Unilateral lesions were produced by a novel method of intracortical microinjection of endothelin-1 (ET-1), intended to principally target the forelimb representation zone in primary motor-primary somatosensory cortex. Lesions were placed in the hemisphere contralateral to the preferred limb and produced deficits in skilled forelimb use on two tasks: the paw reach (PR) test and the foot fault (FF) test. Beginning on post-lesion day (D) 2, animals received injections of 2 mg/kg AMP and were injected every third day until D26. Animals were tested both during, and 24 h after, AMP administration. AMP facilitated recovery of skilled forelimb use on the PR test when assessed during drug-free test sessions. No such effect was seen on the FF test. These results demonstrate that sub-acute administration of AMP following a unilateral focal ischaemic lesion of FL can facilitate task-dependent recovery of skilled forelimb use in the rat. They also demonstrate that different behavioural tasks measuring superficially similar behavioural outputs may show different sensitivities to such drug effects.

Amphetamine↗

PubMed2005

Impaired outcome-specific devaluation of instrumental responding in mice with a targeted deletion of the AMPA receptor glutamate receptor 1 subunit.

The present study evaluated the proposal that mice with a targeted deletion of the glutamate receptor 1 (GluR1) subunit of the AMPA receptor are impaired in using an instrumental or pavlovian signal to gain access to a representation of the sensory-specific motivational properties of a primary reward. In experiment 1, mice were trained to approach two goal boxes in a plus-maze; each goal box contained a different reward (sucrose solution vs food pellet). After acquisition, one of the rewards was devalued by an outcome-specific satiety procedure. Subsequent test trials performed in extinction showed an increase in the latency to enter the devalued goal arm, relative to the nondevalued goal arm in control but not GluR1-/- mice. In experiment 2, a similar outcome-specific satiety procedure was used to examine the effects of reward devaluation on an instrumental nose-poke response. During testing, control but not GluR1-/- mice decreased their rate of responding on a nose poke associated with a devalued reward. A subsequent choice test showed that GluR1-/- mice were able to discriminate between the devalued and nondevalued outcomes used in both experiments. These deficits mirror those seen after lesions of the basolateral amygdala and suggests that GluR1-mediated neurotransmission in this region contributes to encoding the relationship between sensory-specific aspects of reward and their incentive value.

Animals↗

PubMed2004

The role of hippocampal glutamate receptor-A-dependent synaptic plasticity in conditional learning: the importance of spatiotemporal discontiguity.

Gene-targeted mice lacking the AMPA receptor subunit glutamate receptor-A (GluR-A or GluR1) and mice with cytotoxic hippocampal lesions were compared with wild-type and sham-operated controls, respectively, on a conditional learning task using an elevated T-maze. Floor inserts (white perspex vs wire mesh) provided a conditional cue indicating in which goal arm a food reward was to be found. The relationship between the floor insert and the rewarded goal arm was constant throughout the experiment. Both lesioned and knock-out mice were able to acquire the task if the floor inserts extended throughout the entire maze, including the start arm and both goal arms. In contrast, both lesioned and knock-out mice were unable to acquire the task if the floor inserts were only present in the start arm of the maze. The absence of the conditional cue (the floor insert) at the time when the place-reward association was experienced thus critically determined whether or not the mice were impaired. We suggest that hippocampal GluR-A-dependent synaptic plasticity contributes to a memory system in rodents for encoding both the spatial and temporal contexts (the where and the when) associated with a particular event.

Animals↗

PubMed2004

The effects of intracortical endothelin-1 injections on skilled forelimb use: implications for modelling recovery of function after stroke.

Different methods of inducing experimental brain lesions can result in distinct neuropathological sequelae. This could be of consequence in attempts to establish animal models of recovery of function following stroke, as differences in the progression of experimental lesion pathology may have an impact on the magnitude and rate of recovery of function observable with any particular lesioning method. In the present study, a novel method of producing a focal ischaemic lesion by intracortical microinjection of endothelin-1 (ET-1) was compared with excitotoxic (microinjection of quinolinic acid) and mechanical (aspiration) lesioning procedures. Lesions were unilateral and were targeted at the forelimb representation zone in sensorimotor cortex. It was found that all three types of lesion had an essentially identical effect with regard to reaching accuracy in a paw-reaching task. All lesioned animals displayed a similar, significant long-term deficit in reaching accuracy and limited degree of recovery relative to sham animals. Off-line analysis of the performance of animals during post-lesion week 9 indicated that animals in each lesion group also displayed a similar deficit. The current results suggest that the spontaneous behavioural consequences of a unilateral lesion of FL in the rat appear to be independent of the nature of lesion production. However, the increased face validity of an ET-1-induced lesion, coupled with the ease of control of lesion placement and extent offered by this technique make for a potentially important animal model for research into drug effects on recovery of function following stroke.

Animals↗

PubMed2003

Functional specialization within medial frontal cortex of the anterior cingulate for evaluating effort-related decisions.

The rat medial frontal cortex (MFC) has been implicated in allowing animals to work harder to receive larger rewards. However, it is unknown what role the individual MFC regions [anterior cingulate cortex (ACC) and prelimbic-infralimbic cortex (PL-IL)] play in such decision making. To investigate this, we trained rats on a T-maze cost-benefit task with two possible courses of action, shown previously to be affected by complete MFC lesions. One response involved climbing a 30 cm barrier to obtain a large quantity of reward (high cost-high reward), whereas the other had a lower energetic demand but also a smaller reward gain (low cost-low reward). Before surgery, all animals preferred to select the high cost-high reward option. However, after excitotoxic ACC lesions, there was a complete reversal of behavior, with the ACC group selecting the low cost-low reward response on nearly every trial. In contrast, both control animals and rats with PL-IL lesions continued to choose to climb the barrier for the larger reward. When the same rats were tested on a delayed match-to-sample paradigm however, it was the PL-IL group that was significantly impaired at learning the response rule, with the performance of ACC rats being comparable with controls. This double dissociation indicates that the ACC is the important region within the MFC when evaluating how much effort to expand for a specific reward.

Analysis of Variance↗

PubMed2003

A within-subjects, within-task demonstration of intact spatial reference memory and impaired spatial working memory in glutamate receptor-A-deficient mice.

Gene-targeted mice lacking the AMPA receptor subunit glutamate receptor-A (GluRA) (GluR1) and wild-type controls were compared on a radial-maze task in which the same three of six arms were always baited, but in which the rewards of milk were not replaced within a trial. This procedure allowed not only a within-subjects but also a within-trials assessment of both spatial working memory (WM) and reference memory (RM) in GluRA-/- mice, using identical spatial cues. In experiment 1, the GluRA-/- mice made more WM and RM errors during task acquisition. However, separate groups of GluRA-/- and wild-type mice (experiment 2) acquired a purely RM version of the task at a similar rate, using a paradigm with which it was not possible to make WM errors (doors prevented mice from re-entering an arm that they had already visited on that trial). In contrast, mice with hippocampal lesions were dramatically impaired. These results are consistent with the possibility that the WM impairment in the GluRA-/- mice during experiment 1 produced interference that disrupted RM acquisition. A WM component was therefore introduced after RM acquisition in experiment 2 (i.e., the mice were no longer prevented from re-entering a previously visited arm). The GluRA-/- mice now made considerably more WM errors than did wild-type mice, but simultaneously, RM was only mildly and transiently impaired. These experiments provide additional evidence of a selective spatial WM deficit coexisting with intact spatial RM acquisition in GluRA-/- mice, suggesting that different neuronal mechanisms within the hippocampus may support these different kinds of information processing.

Animals↗

PubMed2002

The role of rat medial frontal cortex in effort-based decision making.

We conducted a series of experiments to elucidate the role of rat medial frontal cortex (MFC) (including prelimbic, infralimbic, and cingulate cortices) in effort-based decision making. Rats were trained on a cost-benefit T-maze task in which they could either choose to climb a barrier to obtain a high reward in one arm (HR arm) or could obtain a small reward in the other with no barrier present (LR arm). Before surgery, all animals were selecting the HR arm on almost every trial. However, after excitotoxic lesions to MFC, the rats shifted to selecting the LR arm on almost every trial. This was not caused by a spatial memory or motor deficit because the same rats returned to selecting the HR arm when the amount of effort needed to be expended to obtain reward in either arm was equalized by putting an identical barrier in the LR arm. Additional experiments demonstrated that the change in effort-based decisions observed in the rats was not caused by a complete insensitivity to reward and effort because they returned to choosing the HR arm if either the cost was reduced (by making the barrier smaller) or the benefit was increased (increasing the food ratio differential). Instead, the MFC lesion shifted the animals' decision criterion, making them more likely to choose the LR arm than the sham-lesioned animals. These results imply that medial frontal cortex is important for allowing the animal to put in more work to obtain greater rewards.

Animals↗

PubMed2002

Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery.

Mice received cytotoxic lesions which selectively removed all of the hippocampus and dentate gyrus except the most ventral portions. They were impaired on both spontaneous and rewarded discrete-trial alternation in T-mazes. Acquisition of reference memory for the location of a hidden platform in the Morris water maze was impaired in lesioned mice. On an elevated Y-maze reference memory task, in which only one arm was rewarded, lesioned mice showed no evidence of learning. In a Lashley III maze task, however, where maze rotation demonstrated that control performance was independent of distal spatial cues, acquisition in the lesioned mice was unimpaired. Control levels of continuous spontaneous alternation in a Y-maze were too low to reveal a hippocampal deficit. A small impairment in acquisition of a multiple-trial passive avoidance task was seen in lesioned mice, despite a small but significant increase in reactivity to the footshock. These results are largely consistent with findings in hippocampal lesioned rats on the same or similar tasks, and reflect a major impairment of spatial cognition, with relative sparing of non-spatial task performance.

Animals↗

PubMed2002

Anxiolytic effects of cytotoxic hippocampal lesions in rats.

Rats with cytotoxic lesions of the hippocampus were given 3 anxiety tests: social interaction with a novel rat, the elevated zero-maze (a modification of the plus-maze), and hyponeophagia (eating familiar and novel foods in a novel place). Marked anxiolytic effects were seen in the social interaction and hyponeophagia tests, but not on the zero-maze. These results confirm and extend previous experiments that used traditional lesion techniques. The zero-maze result was consistent with other experiments using the plus-maze, in which intrahippocampal administrations of pharmacological agents were not anxiolytic, although variability in ethological tests may also be a factor. As the hyponeophagia test used an elevated apparatus, as in the zero- and plus-mazes, the lack of a lesion effect in the zero-maze was unlikely to have been due to an inability to relieve height-induced anxiety.

Animals↗