Showing papers by "Michela Gallagher published in 2003"

Different roles for orbitofrontal cortex and basolateral amygdala in a reinforcer devaluation task.

Abstract: The orbitofrontal cortex (OFC) and basolateral amygdala (BLA) are critical for using learned representations of outcomes to guide behavior. Neurophysiological findings suggest complementary roles in which the BLA acquires associations between cues and outcomes and the OFC subsequently uses them to guide behavior. Here, we have used a reinforcer devaluation paradigm to test this hypothesis. In this paradigm, rats are first trained to associate a light conditioned stimulus (CS) with a food outcome, and then the food is devalued by pairing it with illness. After this devaluation procedure, responding to the CS is assessed in a single probe session. Previously, we have shown that BLA and OFC lesions made before training do not affect the acquisition of conditioned responding but do impair the sensitivity of that responding to reinforcer devaluation. Rats with such lesions fail to exhibit the spontaneous decrease in conditioned responding to the light cue observed in controls in the probe test. Here, we have extended those findings by showing that performance in the probe test is impaired by OFC lesions made after light-food conditioning but not by BLA lesions made after that training. These findings indicate that the OFC and BLA play different roles in mediating normal goal-directed performance in this, and likely other, settings. The BLA seems critical to forming representations linking cues to the incentive properties of outcomes but not for maintaining these representations in memory, updating them with new information, or for expressing them in behavior. In contrast, the OFC seems essential for one or more of these latter processes.

Lesions of Orbitofrontal Cortex and Basolateral Amygdala Complex Disrupt Acquisition of Odor-Guided Discriminations and Reversals

Abstract: 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.

Double dissociation of the effects of lesions of basolateral and central amygdala on conditioned stimulus-potentiated feeding and Pavlovian-instrumental transfer.

Abstract: Pavlovian conditioned stimuli (CSs) for food can enhance both the performance of instrumental responses that earn food (Pavlovian-instrumental transfer; PIT) and the consumption of food itself (CS-potentiated feeding). After a single phase of Pavlovian training, each rat was tested in both PIT and potentiated feeding tasks. Rats with lesions of the central nucleus of the amygdala failed to exhibit PIT but showed normal CS-potentiated feeding. By contrast, rats with lesions of the basolateral amygdala showed normal PIT but failed to display CS-potentiated feeding. Performances in a variety of comparison conditions suggested that both lesion effects reflected impairment of acquired motivational functions, rather than with attentional processes or the display of specific learned responses. Implications of the double dissociation of these two aspects of Pavlovian conditioned incentive motivation for amygdala function in associative learning are considered.

Production of new cells in the rat dentate gyrus over the lifespan: relation to cognitive decline

Abstract: The identification of neurogenesis in the dentate gyrus of adult mammals has sparked much interest in a functional role for these new neurons in hippocampal-dependent cognition. The current investigation used a model of age-related cognitive decline in rodents to study the relationship between changes in markers of neurogenesis and hippocampal function. New cell production in the granule cell layer was progressively reduced across the lifespan of male Long Evans rats, with a 40% reduction at middle age (13 months) and a reduction in excess of 80% in advanced age (25 months), compared with young mature adults (7 months). These effects of aging were not, however, predictive of cognitive status. In particular, the pronounced decrease in new cell production during aging did not distinguish among rats that varied over a wide range of cognitive abilities.

Lesions of basolateral amygdala impair extinction of CS motivational value, but not of explicit conditioned responses, in Pavlovian appetitive second-order conditioning

Abstract: The basolateral amygdala (BLA) is important for the modification of the motivational significance of events through associative learning. In previous work, we found that BLA was critical for the acquisition of conditioned reinforcement value to a visual conditioned stimulus (CS) paired with food. Unlike normal rats, rats with neurotoxic lesions of the BLA failed to acquire Pavlovian second-order conditioning to an auditory stimulus paired with the first-order visual CS in the absence of food. In this experiment, we examined the role of BLA in the extinction of the previously acquired conditioned reinforcement value of a Pavlovian CS. Rats received first-order visual CS-food pairings prior to either BLA- or sham-lesions. Subsequent CS-alone extinction training reduced the ability of the visual CS to reinforce second-order conditioning of an auditory stimulus in the sham-lesioned rats, but not in the BLA-lesioned rats. Despite this persistence of the conditioned reinforcement value of the visual first-order CS in the BLA-lesioned rats, no effects of the lesions were observed on extinction of the explicit behavioural conditioned responses elicited by that CS.

Target for therapy of cognitive impairment

Abstract: The invention relates to methods of identifying genes involved in cognitive impairment and compositions for treating cognitive impairment.

Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze

Abstract: Recent evidence has suggested that the relative levels of acetylcholine (ACh) between brain structures may be an important factor in the choice of behavioral strategy in settings in which either hippocampal or dorsal striatal brain systems can be employed both effectively and independently (McIntyre and Gold. 1999. Soc Neurosci Abs 25:1388). The current investigation used the neurotoxin 192 IgG-saporin to deplete the hippocampus of ACh selectively, while leaving ACh in other brain regions, including dorsal striatum, intact. Rats were then trained on a version of the Morris water maze, in which behavioral strategies attributed to the hippocampus and dorsal striatum are placed in direct competition. It was predicted that rats with hippocampal ACh depletion would display a cue bias. Contrary to this prediction, depleting hippocampal ACh did not bias against and, in fact, promoted use of a hippocampal place strategy in this task, as indicated by choice in competition tests and performance on hidden platform training trials. These data add to a growing literature demonstrating that the septohippocampal cholinergic system is not required for accurate spatial learning and suggest a complex role for basal forebrain projections in processing information about the spatial environment.

Aging and hippocampal/cortical circuits in rodents.

Abstract: Behavioral and neurobiologic experiments using healthy aged animals have provided new insight into the brain and age-related memory decline. Specifically, such studies have examined changes in the medial temporal lobe, which includes the hippocampus and interconnected medial temporal cortex, areas that are especially sensitive to the effects of aging and play a critical role in human memory function. The hippocampal system and associated cortical regions in the primate brain receive highly processed information from different sensory modalities. This information converges on the medial temporal cortex and then enters the hippocampus via the entorhinal cortex. A similar scheme of cortical connectivity also exists in the rat brain. In a rat model, Burwell (2000) demonstrated that the perirhinal and postrhinal/parahippocampal cortices in the temporal lobe provide the major polysensory input to the hippocampus via the entorhinal cortex. Similar to the primate, the major pathway of cortical input to the hippocampus derives from layer II of the entorhinal cortex. Cognitive assessments that are sensitive to integrity of the medial temporal lobe system, including the hippocampus, demonstrate behavioral impairments in aged rats compared with young adult rats (Gallagher et al., 1993; Gallagher and Rapp, 1997). A notable feature of the model studied in our research program is individual variability, referring to the fact that not every old animal performs poorly. Within an aged cohort, deficits are apparent for a substantial subgroup of subjects but some aged animals perform on a par with young adult rats. Such animal models, which mirror the phenomenon of variability in decline among elderly humans, indicate that cognitive aging is not inevitable or strictly linked to chronological age. Such models provide the opportunity to compare the changes in the brain that lead to decline or to preserved capacity.

Cible destinee a la therapie d'un trouble cognitif

Abstract: L'invention concerne des procedes d'identification de genes impliques dans un trouble cognitif et des compositions permettant de traiter un tel trouble.