Dorsal hippocampal lesions disrupt Pavlovian delay conditioning and conditioned-response timing

The involvement of the rat dorsal hippocampus (dhpc) in Pavlovian conditioning and timing of conditioned responding was examined in an appetitive preparation in which presentation of a relatively long, 40-s auditory conditioned stimulus (CS) was followed immediately by food delivery. Dorsal hippocampal lesions impaired Pavlovian conditioning in this task. They also produced a deficit in interval timing, replicating previous findings with short CSs. The conditioning and timing deficits observed are consistent with the findings from single-unit recording studies in other species, and suggest that the involvement of the dhpc in Pavlovian processes could be more general than is assumed by many of the current theories of hippocampal function

Dissociations in the effect of delay on object recognition: evidence for an associative model of recognition memory

Rats were administered 3 versions of an object recognition task: In the spontaneous object recognition task (SOR) animals discriminated between a familiar object and a novel object; in the temporal order task they discriminated between 2 familiar objects, 1 of which had been presented more recently than the other; and, in the object-in-place task, they discriminated among 4 previously presented objects, 2 of which were presented in the same locations as in preexposure and 2 in different but familiar locations. In each task animals were tested at 2 delays (5 min and 2 hr) between the sample and test phases in the SOR and object-in-place task, and between the 2 sample phases in the temporal order task. Performance in the SOR was poorer with the longer delay, whereas in the temporal order task performance improved with delay. There was no effect of delay on object-in-place performance. In addition the performance of animals with neurotoxic lesions of the dorsal hippocampus was selectively impaired in the object-in-place task at the longer delay. These findings are interpreted within the framework of Wagner’s (1981) model of memory

Relative recency influences object-in-context memory

In two experiments rats received training on an object-in-context (OIC) task, in which they received preexposure to object A in context x, followed by exposure to object B in context y. In a subsequent test both A and B are presented in either context x or context y. Usually more exploration is seen of the object that has not previously been paired with the test context, an effect attributed to the ability to remember where an object was encountered. However, in the typical version of this task, object A has also been encountered less recently than object B at test. This is precisely the arrangement in tests of ‘relatively recency’ (RR), in which more remotely presented objects are explored more than objects experienced more recently. RR could contaminate performance on the OIC task, by enhancing the OIC effect when animals are tested in context y, and masking it when the test is in context x. This possibility was examined in two experiments, and evidence for superior performance in context y was obtained. The implications of this for theoretical interpretations of recognition memory and the procedures used to explore it are discussed

Effects of dorsal hippocampal damage on conditioning and conditioned-response timing: a pooled analysis

Behavioral findings suggest that the dorsal hippocampus (DHPC) plays a role in timing of appetitive conditioned responding. The present article explored the relationship between the extent of DHPC damage and timing ability, in a pooled analysis of three published studies from our laboratory. Initial analyses of variance confirmed our previous reports that DHPC damage reduced peak time (a measure of timing accuracy). However, the spread (a measure of timing precision) was unchanged, such that the coefficient of variation (spread/peak time) was significantly larger in DHPC-lesioned animals. This implies that, in addition to the well-established effect of DHPC lesions on timing accuracy, DHPC damage produced a deficit in precision of timing. To complement this analysis, different generalized linear mixed-effects models (GLMMs) were performed on the combined dataset, to examine which combinations of the different behavioral measures of timing were the best predictors of the degree of hippocampal damage. The results from the GLMM analysis suggested that the greater the DHPC damage, the greater the absolute difference between the observed peak time and reinforced duration. Nevertheless, this systematic relationship between damage and performance was not specific to the temporal domain: paradoxically the greater the damage the greater the magnitude of peak responding. We discuss these lesion effects in terms of scalar timing theory

Dim Light in the Evening Causes Coordinated Realignment of Circadian Rhythms, Sleep, and Short-Term Memory

Light provides the primary signal for entraining circadian rhythms to the day/night cycle. In addition to rods and cones, the retina contains a small population of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). Concerns have been raised that exposure to dim artificial lighting in the evening (DLE) may perturb circadian rhythms and sleep patterns, and OPN4 is presumed to mediate these effects. Here, we examine the effects of 4-h, 20-lux DLE on circadian physiology and behavior in mice and the role of OPN4 in these responses. We show that 2 wk of DLE induces a phase delay of ∼2 to 3 h in mice, comparable to that reported in humans. DLE-induced phase shifts are unaffected in Opn4-/- mice, indicating that rods and cones are capable of driving these responses in the absence of melanopsin. DLE delays molecular clock rhythms in the heart, liver, adrenal gland, and dorsal hippocampus. It also reverses short-term recognition memory performance, which is associated with changes in preceding sleep history. In addition, DLE modifies patterns of hypothalamic and cortical cFos signals, a molecular correlate of recent neuronal activity. Together, our data show that DLE causes coordinated realignment of circadian rhythms, sleep patterns, and short-term memory process in mice. These effects are particularly relevant as DLE conditions-due to artificial light exposure-are experienced by the majority of the populace on a daily basis

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background