Rosiglitazone improves contextual fear conditioning in aged rats.

Experimental, clinical, and epidemiologic studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) are beneficial in Alzheimer's disease and other neuroinflammatory processes. One possible mechanism is an interaction with peroxisome proliferator-activated receptors (PPARs). We examined the effect of a specific PPARgamma agonist, rosiglitazone, on contextual fear conditioning in aged rats. Male rats (20-months-old) were administered rosiglitazone in the diet for 2 months prior to behavioral testing. Young control and aged rats fed rosiglitazone froze significantly more than did the aged control rats in a hippocampal-dependent fear conditioning task. Rosiglitazone had no effect hippocampal interleukin-1beta levels, markers of oxidative damage, and NMDA receptor expression. Therefore, activation of PPARgamma prevented age-related deficits in hippocampal function.

Exploring variability and sources of measurement error in alcohol expectancy questionnaire reliability coefficients: a meta-analytic reliability generalization study.

OBJECTIVE: Reliability Generalization, a relatively new meta-analytic score reliability technique, was used to examine reliability coefficients for Alcohol Expectancy Questionnaire (AEQ) subscales in published research. Specifically, the present study identified the typical reliability coefficients of scores on AEQ subscales across published studies and examined sources of measurement error across AEQ subscales and studies. METHOD: Based on literature reviews of PsyclNFO and PubMed, a total of 71 studies were analyzed and coded on 10 different dimensions believed to affect score reliability. RESULTS: Only 37% of the studies surveyed reported reliability coefficients for the data in hand. Analysis of these studies revealed that the average score reliability across studies varied considerably in subscales and samples, with the Arousal/Interpersonal Power and Sexual Enhancement subscales evidencing the greatest variability. Gender homogeneity and racial homogeneity were found to be the two most important predictors of the magnitude of score reliability coefficients across subscales and studies. CONCLUSIONS: Results of the study indicate that the AEQ tends to generate reliable scores, with some noted exceptions. Because the Arousal/Interpersonal Power and Sexual Enhancement subscales tend to generate unacceptably low reliability coefficients and because the AEQ holds promise in furthering prevention and treatment outcome research, it is suggested that future research with the AEQ explore instrument factor structure and item consistency. Because reliability estimates can influence substantive statistical analyses, it is recommended that authors using the AEQ report reliability information in their published work.

Adult plasticity of spatiotemporal receptive fields of multisensory superior colliculus neurons following early visual deprivation.

PURPOSE: Previous work has established that the integrative capacity of multisensory neurons in the superior colliculus (SC) matures over a protracted period of postnatal life (Wallace and Stein, 1997), and that the development of normal patterns of multisensory integration depends critically on early sensory experience (Wallace et al., 2004). Although these studies demonstrated the importance of early sensory experience in the creation of mature multisensory circuits, it remains unknown whether the reestablishment of sensory experience in adulthood can reverse these effects and restore integrative capacity. METHODS: The current study tested this hypothesis in cats that were reared in absolute darkness until adulthood and then returned to a normal housing environment for an equivalent period of time. Single unit extracellular recordings targeted multisensory neurons in the deep layers of the SC, and analyses were focused on both conventional measures of multisensory integration and on more recently developed methods designed to characterize spatiotemporal receptive fields (STRF). RESULTS: Analysis of the STRF structure and integrative capacity of multisensory SC neurons revealed significant modifications in the temporal response dynamics of multisensory responses (e.g., discharge durations, peak firing rates, and mean firing rates), as well as significant changes in rates of spontaneous activation and degrees of multisensory integration. CONCLUSIONS: These results emphasize the importance of early sensory experience in the establishment of normal multisensory processing architecture and highlight the limited plastic potential of adult multisensory circuits.

Spatial receptive field organization of multisensory neurons and its impact on multisensory interactions.

Previous work has established that the spatial receptive fields (SRFs) of multisensory neurons in the cerebral cortex are strikingly heterogeneous, and that SRF architecture plays an important deterministic role in sensory responsiveness and multisensory integrative capacities. The initial part of this contribution serves to review these findings detailing the key features of SRF organization in cortical multisensory populations by highlighting work from the cat anterior ectosylvian sulcus (AES). In addition, we have recently conducted parallel studies designed to examine SRF architecture in the classic model for multisensory studies, the cat superior colliculus (SC), and we present some of the preliminary observations from the SC here. An examination of individual SC neurons revealed marked similarities between their unisensory (i.e., visual and auditory) SRFs, as well as between these unisensory SRFs and the multisensory SRF. Despite these similarities within individual neurons, different SC neurons had SRFs that ranged from a single area of greatest activation (hot spot) to multiple and spatially discrete hot spots. Similar to cortical multisensory neurons, the interactive profile of SC neurons was correlated strongly to SRF architecture, closely following the principle of inverse effectiveness. Thus, large and often superadditive multisensory response enhancements were typically seen at SRF locations where visual and auditory stimuli were weakly effective. Conversely, subadditive interactions were seen at SRF locations where stimuli were highly effective. Despite the unique functions characteristic of cortical and subcortical multisensory circuits, our results suggest a strong mechanistic interrelationship between SRF microarchitecture and integrative capacity.

Blockade of caspase-1 increases neurogenesis in the aged hippocampus.

Adult hippocampal neurogenesis dramatically decreases with increasing age, and it has been proposed that this decline contributes to age-related memory deficits. Central inflammation contributes significantly to the decrease in neurogenesis associated with ageing. Interleukin-1beta is a proinflammatory cytokine initially synthesized as an inactive precursor that is cleaved by caspase-1 to generate the biologically active mature form. Whether IL-1beta affects neurogenesis in the aged hippocampus is unknown. Here we analysed cells positive for 5-bromo-2-deoxyuridine (BrdU; 50 mg/kg) in animals in which cleavage of IL-1beta was inhibited by the caspase-1 inhibitor Ac-YVAD-CMK (10 pmol). Aged (22 months) and young (4 months) rats received Ac-YVAD-CMK for 28 days intracerebroventricularly through a brain infusion cannula connected to an osmotic minipump. Starting on day 14, animals received a daily injection of BrdU for five consecutive days. Unbiased stereology analyses performed 10 days after the last injection of BrdU revealed that the total number of newborn cells generated over a 5-day period was higher in young rats than in aged rats. In addition, there was a 53% increase in the number of BrdU-labelled cells of the aged Ac-YVAD-CMK-treated rats compared to aged controls. Immunofluorescence studies were performed to identify the cellular phenotype of BrdU-labelled cells. The increase in BrdU-positive cells was not due to a change in the proportion of cells expressing neuronal or glial phenotypes in the subgranular zone. These findings demonstrate that the intracerebroventricular administration of Ac-YVAD-CMK reversed the decrease in hippocampal neurogenesis associated with ageing.

Improvement of memory for context by inhibition of caspase-1 in aged rats.

Impaired learning and memory is a common pathologic feature associated with numerous neurologic disorders. There is strong evidence that central inflammation contributes significantly to the progression of several neurodegenerative diseases as well as to the ageing process. For example, in aged rats an increase in interleukin-1beta (IL-1beta) is implicated in the decline of synaptic plasticity in the hippocampus and impaired performance on cognitive tasks such as contextual fear conditioning. IL-1beta is a proinflammatory cytokine initially synthesized in an inactive precursor form that is cleaved by caspase-1 to generate the biologically mature form. In the present study, cleavage of IL-1beta was chronically inhibited using a specific caspase-1 inhibitor (Ac-YVAD-CMK; 10 pmol) in both aged (22 month) and young (4 month) rats. Both groups received Ac-YVAD-CMK for 28 days intracerebroventricularly through a brain infusion cannula connected to an osmotic minipump. On day 20 the animals were trained in contextual fear conditioning, and memory for context was tested on day 22. Chronic infusion of a specific caspase-1 inhibitor in aged rats ameliorated age-related increases in hippocampal IL-1beta and improved memory for context.