Biomedical subjects

David J Bucci

Publications and source records attributed to David J Bucci.

12 recordsLinked to original sources

PubMed2006

Central nicotinic cholinergic systems: a role in the cognitive dysfunction in attention-deficit/hyperactivity disorder?

Theories of the neurobiological basis of Attention-Deficit/Hyperactivity Disorder (ADHD) have largely focused on dysregulation of central dopaminergic function. However, other neurotransmitter systems may be implicated in specific cognitive deficits in ADHD. Interest in the potential involvement of nicotinic cholinergic systems in ADHD has arisen in part from the observation that adolescents and adults with ADHD smoke cigarettes at significantly higher rates than people without this disorder. In addition, several studies report that nicotine alleviates ADHD symptoms, and recent neuro-genetics studies indicate that cholinergic systems may be altered in persons with ADHD. In this review, we describe the evidence for a role of central nicotinic cholinergic systems in cognitive deficits in ADHD. We also propose mechanisms by which alterations in cholinergic function may contribute directly and/or indirectly to these deficits. Finally, we identify specific paradigms and models to guide future investigations into the specific involvement of nicotinic cholinergic systems in ADHD, possibly leading to the development of more effective pharmacotherapies for ADHD.

Animals↗

PubMed2006

Nicotine administration enhances conditioned inhibition in rats.

The effect of nicotine on conditioned inhibition was examined using a serial feature negative discrimination task. Nicotine (0.35 mg/kg) or vehicle was administered before each of the 16 training sessions. On some trials in each session, a tone was presented and followed by food reward. On other trials, the tone was preceded by a visual stimulus and not reinforced. Nicotine-treated rats exhibited greater discrimination between the two trial types as evidenced by less frequent responding during non-reinforced trials, and learned the discrimination in fewer sessions than vehicle-treated rats. In contrast, there were no group differences in responding during the reinforced trials.

Analysis of Variance↗

PubMed2006

Elevations of endogenous kynurenic acid produce spatial working memory deficits.

Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the alpha7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed.

Animals↗

PubMed2006

Blockade of cannabinoid CB1 receptors alters contextual learning and memory.

The endocannabinoid system appears to have an important role in specific aspects of learning and memory, yet there has been no systematic study of the role of cannabinoid receptors in contextual fear conditioning. The present study examined the effects of cannabinoid CB(1) receptor blockade on the acquisition, consolidation, and expression of contextual fear using the selective cannabinoid CB(1) receptor antagonist AM251. AM251 produced a decrease in the expression of contextual fear when administered prior to training, testing, or both. This effect was observed when footshock was signaled by an auditory cue but not in an unsignaled shock version of the task. Moreover, blocking cannabinoid CB(1) receptors had no effect on consolidation of contextual memory regardless of the conditioning paradigm. These data indicate that inhibition of cannabinoid CB(1) receptors produces specific deficits in processing contextual information and that the effects of CB(1) antagonists on contextual learning may differ from effects on other types of learning.

Animals↗

PubMed2006

Increased concentration of cerebral kynurenic acid alters stimulus processing and conditioned responding.

Kynurenic acid (KYNA) is a tryptophan metabolite synthesized and released by glia and recently shown to be a non-competitive antagonist of alpha7 nicotinic acetylcholine receptors at physiologically relevant concentrations, and NMDA receptors at higher concentrations. KYNA concentration is elevated in individuals with schizophrenia and those with Alzheimer's disease, two populations exhibiting cholinergic-related cognitive impairments. The present study investigated the effects of elevated KYNA concentration on conditioned stimulus processing in rats. For the first 2 days of the experiment, a subset of rats received intracerebroventricular infusions of either KYNA (0.1 microM) or vehicle and were either returned to the home cage or received non-reinforced presentations of a visual stimulus. All rats subsequently received presentations of the same visual stimulus followed by food reward during a 6-day training phase. In vehicle-treated rats, pre-exposure to the visual stimulus reduced orienting behaviour to the light (standing on the hind legs and orienting towards the visual stimulus) when it was later reinforced (i.e., conditioned orienting). In contrast, pre-exposure to the visual cue or 2 days of KYNA pretreatment reduced conditioned orienting behaviour. Finally, the reduction of orienting in KYNA-treated rats following pre-exposure was not as robust as in vehicle-treated rats. These results suggest that elevated KYNA levels can alter specific aspects of attentional processing of environmental stimuli and are discussed in terms of the potential contribution of KYNA to cognitive function and dysfunction.

Analysis of Variance↗

PubMed2005

Arousal from hibernation alters contextual learning and memory.

Hibernation is a unique and highly regulated physiological state characterized by profound, albeit periodically reversible, depression in body temperature, metabolism, and consciousness. Hippocampal synapses undergo pronounced remodeling in concert with torpor and arousal. During hibernation, the number of postsynaptic densities, apical dendritic branches, and spine densities decreases substantially in the hippocampus. Upon arousal these parameters increase beyond pre-hibernation levels and peak within 2-3h. By 24h after arousal, dendritic parameters remain elevated but have started to subside, consistent with pruning and differentiation. The present study examined the functional consequences of these natural changes in synaptic structure. Wild-caught Arctic ground squirrels (AGS) were trained in a hippocampal-dependent contextual fear conditioning task at 3h, 24h, or 4 weeks after arousal (warm-adapted euthermic control group). All groups acquired the fear conditioned response similarly on the training day. During a subsequent retention test session, AGS in the 24h group exhibited enhanced expression of contextual fear compared to the other two groups. These data suggest that the morphological and biochemical changes occurring at 24h after arousal from hibernation affect hippocampal-dependent learning and memory. The natural change in synaptic structure during hibernation may provide a unique opportunity to assess the neural substrates underlying cognitive enhancement.

Analysis of Variance↗

PubMed2005

Stimulus processing and associative learning in Wistar and WKHA rats.

This study assessed basic learning and attention abilities in Wistar-Kyoto hyperactive (WKHA) rats using appetitive conditioning preparations. Two measures of conditioned responding to a visual stimulus, orienting behavior (rearing on the hind legs), and food cup behavior (placing the head inside the recessed food cup) were measured. In Experiment 1, simple conditioning, but not extinction, was impaired in WKHA rats compared with Wistar rats. In Experiment 2, nonreinforced presentations of the visual cue preceded the conditioning sessions. WKHA rats displayed less orienting behavior than Wistar rats but comparable levels of food cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in attentional processing as well as in learning stimulus-reward relationships.

Animals↗

PubMed2005

Specific changes in conditioned responding following neurotoxic damage to the posterior parietal cortex.

The central nucleus (CN) of the amygdala and basal forebrain cholinergic projections to the posterior parietal cortex (PPC) are involved in regulating changes in attentional processing of conditioned stimuli. In a previous study, lesions of the CN produced a deficit in conditioned orienting behavior (rearing on the hind legs) when a visual stimulus was paired with food. Unconditioned orienting (rearing to nonreinforced presentations of the stimulus) and conditioned food cup behavior were unaffected. The present study examined the contribution of the PPC to attentional orienting behavior. Damage to the PPC did not affect orienting behavior but produced deficits in food cup behavior. These findings help define the specific contributions of the PPC to attentional processing and associative learning.

Analysis of Variance↗

PubMed2004

Perirhinal and postrhinal contributions to remote memory for context.

The perirhinal (PER) and postrhinal (POR) cortices, two components of the medial temporal lobe memory system, are reciprocally connected with the hippocampus both directly and via the entorhinal cortex. Damage to PER or POR before or shortly after training on a contextual fear conditioning task causes deficits in the subsequent expression of contextual fear, implicating these regions in the acquisition or expression of contextual memory. Here, we examined the contribution of PER and POR to the processing of remotely learned contextual information. Male Long-Evans rats were trained in an unsignaled contextual fear conditioning paradigm. After training, rats received bilateral neurotoxic lesions to PER or POR or sham control surgeries at three different training-to-lesion intervals: 1, 28, or 100 d after training. Two weeks after surgery, lesioned and control rats were returned to the training context to assess contextual fear as measured by freezing. Rats with PER or POR damage froze significantly less in the training context than control rats but were not different from each other. The severity of the deficit did not differ across training-to-lesion intervals for any group. This pattern of deficits differs from that of posttraining hippocampal lesions, for which longer training-to-lesion intervals produce significantly more fear-conditioned contextual freezing than shorter training-to-lesion intervals. In the absence of such a retrograde gradient in the present study, our interpretation is that PER and POR have an ongoing role in the storage or retrieval of representations for context. Alternatively, these regions may be involved in a more extended consolidation process that becomes apparent beyond 100 d after learning.

Animals↗

PubMed2004

Corticohippocampal contributions to spatial and contextual learning.

Spatial and contextual learning are considered to be dependent on the hippocampus, but the extent to which other structures in the medial temporal lobe memory system support these functions is not well understood. This study examined the effects of individual and combined lesions of the perirhinal, postrhinal, and entorhinal cortices on spatial and contextual learning. Lesioned subjects were consistently impaired on measures of contextual fear learning and consistently unimpaired on spatial learning in the Morris water maze. Neurotoxic lesions of perirhinal or postrhinal cortex that were previously shown to impair contextual fear conditioning (Bucci et al., 2000) or contextual discrimination (Bucci et al., 2002) caused little or no impairment in place learning and incidental learning in the water maze. Combined lesions of perirhinal plus lateral entorhinal or postrhinal plus medial entorhinal cortices resulted in deficits in acquisition of contextual discrimination but had no effect on place learning in the water maze. Finally, a parahippocampal lesion comprising combined neurotoxic damage to perirhinal, postrhinal, and entorhinal cortices resulted in profound impairment in acquisition of a standard passive avoidance task but failed to impair place learning. In the same experiment, rats with hippocampal lesions were impaired in spatial navigation. These results indicate that tasks requiring the association between context and an aversive stimulus depend on corticohippocampal circuitry, whereas place learning in the water maze can be accomplished without the full complement of highly processed information from the cortical regions surrounding the hippocampus. The evidence that different brain systems underlie spatial navigation and contextual learning has implications for research on memory when parahippocampal regions are involved.

Animals↗

PubMed2004

Deficits in attentional orienting following damage to the perirhinal or postrhinal cortices.

The authors used an associative learning paradigm to assess the effects of perirhinal or postrhinal damage on attentional orienting. Control rats and rats with lesions of either the perirhinal or postrhinal cortex initially displayed high levels of orienting behavior (rearing) to presentations of a light cue. Continued nonreinforced presentations resulted in normal habituation of the response. In addition, orienting reemerged in control rats, indicating increased attentional processing of the cue. This conditioned orienting did not reemerge in rats with either perirhinal or postrhinal lesions, providing direct evidence that the rat perirhinal and postrhinal cortices each play a role in attention. These results are consistent with an emerging view that some structures within the medial temporal lobe have nonmnemonic functions.

Animals↗

PubMed2002

Contextual fear discrimination is impaired by damage to the postrhinal or perirhinal cortex.

Postrhinal (POR) or perirhinal (PER) cortex damage impairs acquisition and expression of contextual fear, but the nature of the impairment remains unclear. This study used a contextual fear discrimination paradigm that biased subjects toward using a configural, rather than an elemental, strategy to distinguish between 2 contexts, I of which was paired with a mild footshock. Control rats discriminated between 2 contexts when a combination of several cues could be used (Experiment 1), but not when individual sensory cues were manipulated (Experiment 2). Rats with POR or PER lesions could not discriminate between the shock and no-shock contexts when multiple cues differentiated the contexts (Experiment 3). The results indicate that both the POR and PER have a role in configural learning of contextual fear.

Animals↗