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Biomedical subjects

Michela Gallagher

Publications and source records attributed to Michela Gallagher.

44 records · Page 3Linked to original sources
PubMed2002

Disconnection of the basolateral amygdala complex and nucleus accumbens impairs appetitive pavlovian second-order conditioned responses.

There is considerable evidence that the basolateral complex of the amygdala (ABL) is involved in learning about the motivational value of otherwise neutral stimuli. The authors examined the role in this function of the ABL and one of its major efferent structures. the nucleus accumbens. Male Long-Evans rats received either sham, ipsilaterally, or contralaterally placed unilateral lesions of the ABL and accumbens and were trained in an appetitive Pavlovian second-order conditioning task. Sham-lesioned and ipsilaterally lesioned rats acquired the task normally, but contralaterally lesioned rats, in which the ABL and accumbens were functionally disconnected, failed to acquire second-order conditioned responses (although they did acquire second-order conditioned orienting responses). The results suggest that the ABL and accumbens are part of a system critical for processing information about learned motivational value.

Amygdala↗
PubMed2002

The basolateral complex of the amygdala is necessary for acquisition but not expression of CS motivational value in appetitive Pavlovian second-order conditioning.

The basolateral complex of the amygdala (ABL) is involved in processing information about stimulus motivational value. However, it is not clear whether the ABL is critical for acquisition, maintenance, or expression of this information. Our previous work has shown that ABL lesions made prior to training, block acquisition of an appetitive Pavlovian second-order conditioning task, in which performance is thought to depend on the acquisition of motivational (conditioned reinforcement) value by the first-order conditioned stimulus (CS). The present experiments examined the effects of ABL lesions made after first-order conditioning, when the CS acquires motivational value, but before second-order conditioning, the test for acquired value of that CS. Rats received pairings of a visual CS with a food reinforcer. They then received bilateral sham or excitotoxic lesions of the ABL. After recovery, they received pairings of a second-order auditory CS with the previously conditioned visual CS. In two experiments, both sham and lesioned rats acquired normal second-order conditioned behaviours. Some of the same rats were then given another round of second-order conditioning with novel CSs. In this case, when first-order training occurred after surgery, some second-order conditioned behaviours were impaired in lesioned rats. Tests of the associative underpinnings of second-order conditioned behaviours showed that those behaviours impaired by ABL lesions were based on stimulus-response associations. The results show that although the ABL is critical for second-order conditioning, this role is limited to acquisition of information about the motivational value of the first-order CS, and it is not critical for maintenance of this information or for its use in forming second-order associations.

Acoustic Stimulation↗
PubMed2002

Decreased glucocorticoid receptor mRNA and dysfunction of HPA axis in rats after removal of the cholinergic innervation to hippocampus.

Excess exposure to glucocorticoids can have deleterious effects on physiology and cognition. Glucocorticoids acting via receptors located in hippocampal neurons contribute to negative feedback after stress by terminating the further release of glucocorticoids. The current study investigated the effects of selective immunolesions of septo-hippocampal cholinergic neurons on hippocampal corticosterone receptor mRNA and on hypothalamic-pituitary-adrenal (HPA) activity. As evaluated by in situ hybridization, hippocampal glucocorticoid receptor (GR) mRNA, but not mineralocorticoid receptor (MR) mRNA, was significantly decreased in lesioned rats compared to controls. In a companion study, the peak corticosterone response to one hour of restraint stress did not differ between lesion and control groups but the post-stress decline of corticosterone was more protracted in the lesioned rats. These findings are discussed in terms of their possible relevance to ageing as age-related degeneration of the basal forebrain cholinergic system may contribute to the commonly observed dysfunction of the HPA axis in older animals.

Animals↗
PubMedDate not supplied

Transcriptional mechanisms of hippocampal aging.

Aging related cognitive decline is an increasing health problem but affects only a subset of elderly humans. This research uses outbred young (Y) and aged rats. Behavioral characterization distinguishes aged rats with impaired spatial learning (AI) and aged rats with unimpaired learning ability (AU), mimicking the varied susceptibility of the human population to age-associated learning impairment. Studies are testing a hypothesis that hippocampal transcriptional mechanisms and gene expression profiles linked to activator protein-1 (AP-1) and glucocorticoid receptor (GR), mineralocorticoid receptor (MR) or cyclic AMP response element binding protein (CREB) families of transcription factors distinguish successful or unsuccessful aging and cognition. Results from mRNA assays, in situ hybridization, electromobility shift assays and western immunoblot indicate changes in GR and CREB in AI rats. State of the art future approaches to define downstream transcription targets are described.

Aging↗
PubMedDate not supplied

Teaching old rats new tricks: age-related impairments in olfactory reversal learning.

Recent work suggests that normal aging may be associated with decline in different brain systems. In the present study, young and aged Long-Evans rats were tested in a spatial version of the Morris water maze dependent on medial temporal lobe function and also on an odor discrimination reversal task previously used to investigate orbitofrontal function. Aged rats acquired the odor discrimination problems normally but were impaired in acquiring subsequent reversals of the problems. A subset of the aged rats also exhibited impaired spatial learning in the water maze. There was no correlation between reversal performance and spatial learning in the aged rats, indicating that the reversal learning impairment was not related to decline in medial temporal lobe function. Instead the performance of the aged rats on the odor discrimination task resembled that of young rats with neurotoxic lesions of orbitofrontal cortex. These data indicate that rats show independent decline of different brain systems during normal aging and suggest orbitofrontal cortex as one prefrontal area where changes may be localized for further study.

Aging↗
PubMedDate not supplied

Effects of aging on the hippocampal formation in a naturally occurring animal model of mild cognitive impairment.

Vertical integration is being used to great advantage in neurobiological research on the basis of age-related cognitive decline. Such research bridges analysis between the molecular and cellular levels and the outcome of impaired psychological functions. Current use of animals models within this paradigm has defined mild cognitive impairment in a subpopulation of outbred aged Long-Evans rats by assessment of hippocampal-dependent spatial cognition. Aged rats with cognitive impairment exhibited no loss of neurons in the hippocampus. Current research is focused on the functional alterations in neurons by methods which assess transcriptional mechanisms and signaling pathways.

Aging↗
PubMedDate not supplied

Lesions of orbitofrontal cortex and basolateral amygdala complex disrupt acquisition of odor-guided discriminations and reversals.

Recent work indicates that both orbitofrontal cortex (OFC) and the basolateral complex of the amygdala (ABL) are involved in processes by which cues are associated with predicted outcomes. To examine the respective roles of these structures in discrimination learning, rats with bilateral sham or neurotoxic lesions of either OFC or ABL were trained on a series of four 2-odor discrimination problems in a thirst-motivated go, no-go task. After acquisition of the series of odor problems, the rats were trained on serial reversals of the final odor problem. Performance on each problem was assessed by monitoring accuracy of choice behavior, and also by measuring latency to respond for fluid outcomes after odor sampling. During discrimination learning, rats in both lesioned groups had similar deficits, failing to show normal changes in response latency during learning, while at the same time exhibiting normal choice behavior relative to controls. Choice behavior was affected only during the reversal phase of training, in which OFC and ABL lesions produced distinctive deficits. Rats with ABL lesions were impaired on the first reversal (S1-/S2+), but were unimpaired at acquiring a reversal back to the original odor-outcome contigencies (S1+/S2-), whereas rats with OFC lesions were impaired on both types of reversals. These findings suggest that OFC and ABL serve partially overlapping roles in the use of incentive information that supports normal discrimination performance.

Amygdala↗