Perirhinal cortex and the recognition of relative familiarity

Spontaneous object recognition (SOR) is a widely used task of recognition memory in rodents which relies on their propensity to explore novel (or relatively novel) objects. Network models typically define perirhinal cortex as a region required for recognition of previously seen objects largely based on findings that lesions or inactivations of this area produce SOR deficits. However, relatively little is understood about the relationship between the activity of cells in the perirhinal cortex that signal novelty and familiarity and the behavioural responses of animals in the SOR task. Previous studies have used objects that are either highly familiar or absolutely novel, but everyday memory is for objects that sit on a spectrum of familiarity which includes objects that have been seen only a few times, or objects that are similar to objects which have been previously experienced. We present two studies that explore cellular activity (through c-fos imaging) within perirhinal cortex of rats performing SOR where the familiarity of objects has been manipulated. Despite robust recognition memory performance, we show no significant changes in perirhinal activity related to the level of familiarity of the objects. Reasons for this lack of familiarity-related modulation in perirhinal cortex activity are discussed. The current findings support emerging evidence that perirhinal responses to novelty are complex and that task demands are critical to the involvement of perirhinal cortex in the control of object recognition memory

Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism.Corinne Caillaud, Mie Mechta, Heidi Ainge, Andreas N Madsen, Patricia Ruell, Emilie Mas, Catherine Bisbal, Jacques Mercier, Stephen Twigg, Trevor A Mori, David Simar and Romain Barrè

Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies

Understanding the mechanisms whereby information encoded within patterns of action potentials is deciphered by neurons is central to cognitive psychology. The multiprotein complexes formed by NMDA receptors linked to synaptic membrane-associated guanylate kinase (MAGUK) proteins including synapse-associated protein 102 (SAP102) and other associated proteins are instrumental in these processes. Although humans with mutations in SAP102 show mental retardation, the physiological and biochemical mechanisms involved are unknown. Using SAP102 knock-out mice, we found specific impairments in synaptic plasticity induced by selective frequencies of stimulation that also required extracellular signal-regulated kinase signaling. This was paralleled by inflexibility and impairment in spatial learning. Improvement in spatial learning performance occurred with extra training despite continued use of a suboptimal search strategy, and, in a separate nonspatial task, the mutants again deployed a different strategy. Double-mutant analysis of postsynaptic density-95 and SAP102 mutants indicate overlapping and specific functions of the two MAGUKs. These in vivo data support the model that specific MAGUK proteins couple the NMDA receptor to distinct downstream signaling pathways. This provides a mechanism for discriminating patterns of synaptic activity that lead to long-lasting changes in synaptic strength as well as distinct aspects of cognition in the mammalian nervous system

Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease

This study was supported by grants from National Institute of Health Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS) . F.G.-M. and J.A. were supported by the Alzheimer’s Research UK, the RS MacDonald Charitable Trust, and the BRAINS 600th Anniversary fund S.S.Y received Howard Mossberg Distinguished Professorship endowment from the University of Kansas.Endophilin A1 (EP) is a protein enriched in synaptic terminals that has been linked to Alzheimer’s disease (AD). Previous in vitro studies have shown that EP can bind to a variety of proteins, which elicit changes in synaptic transmission of neurotransmitters and spine formation. Additionally, we previously showed that EP protein levels are elevated in AD patients and AD transgenic animal models. Here, we establish the in vivo consequences of upregulation of EP expression in amyloid-β peptide (Aβ)-rich environments, leading to changes in both long-term potentiation and learning and memory of transgenic animals. Specifically, increasing EP augmented cerebral Aβ accumulation. EP-mediated signal transduction via reactive oxygen species (ROS)/p38 mitogen-activated protein (MAP) kinase contributes to Aβ-induced mitochondrial dysfunction, synaptic injury, and cognitive decline, which could be rescued by blocking either ROS or p38 MAP kinase activity.Publisher PDFPeer reviewe

The Influence of Markov Decision Process Structure on the Possible Strategic Use of Working Memory and Episodic Memory

Researchers use a variety of behavioral tasks to analyze the effect of biological manipulations on memory function. This research will benefit from a systematic mathematical method for analyzing memory demands in behavioral tasks. In the framework of reinforcement learning theory, these tasks can be mathematically described as partially-observable Markov decision processes. While a wealth of evidence collected over the past 15 years relates the basal ganglia to the reinforcement learning framework, only recently has much attention been paid to including psychological concepts such as working memory or episodic memory in these models. This paper presents an analysis that provides a quantitative description of memory states sufficient for correct choices at specific decision points. Using information from the mathematical structure of the task descriptions, we derive measures that indicate whether working memory (for one or more cues) or episodic memory can provide strategically useful information to an agent. In particular, the analysis determines which observed states must be maintained in or retrieved from memory to perform these specific tasks. We demonstrate the analysis on three simplified tasks as well as eight more complex memory tasks drawn from the animal and human literature (two alternation tasks, two sequence disambiguation tasks, two non-matching tasks, the 2-back task, and the 1-2-AX task). The results of these analyses agree with results from quantitative simulations of the task reported in previous publications and provide simple indications of the memory demands of the tasks which can require far less computation than a full simulation of the task. This may provide a basis for a quantitative behavioral stoichiometry of memory tasks

Odor supported place cell model and goal navigation in rodents

Experiments with rodents demonstrate that visual cues play an important role in the control of hippocampal place cells and spatial navigation. Nevertheless, rats may also rely on auditory, olfactory and somatosensory stimuli for orientation. It is also known that rats can track odors or self-generated scent marks to find a food source. Here we model odor supported place cells by using a simple feed-forward network and analyze the impact of olfactory cues on place cell formation and spatial navigation. The obtained place cells are used to solve a goal navigation task by a novel mechanism based on self-marking by odor patches combined with a Q-learning algorithm. We also analyze the impact of place cell remapping on goal directed behavior when switching between two environments. We emphasize the importance of olfactory cues in place cell formation and show that the utility of environmental and self-generated olfactory cues, together with a mixed navigation strategy, improves goal directed navigation

A systematic review on animal models of maternal high fat feeding and offspring glycaemic control

The mechanistic link between obese parents and obese offspring and the relative role of genes, and a shared environment is not completely understood. Animal models help us to differentiate between genetic and environmental factors, and the interaction between the two. However, the willingness of researchers to blend results from multiple models makes it difficult for clear mechanisms to be identified for specific hypothesis-driven research. As such we conducted a systematic review of animal models of maternal high fat feeding in an effort to identify the affect on the offspring glycaemic control. Maternal and offspring outcomes are reported in an effort to identify possible relationships to facilitate and focus on future research. We present here data from 11 studies investigating glycaemic control in offspring exposed to a high fat diet (HFD) during maternal gestation only or gestation and lactation. Studies in this review identify a real risk of type 2 diabetes and obesity in male offspring exposed to a maternal HFD. Poor glycaemic control in the offspring appears to be independent of maternal obesity, birth weight or post-weaning macronutrient intake. Inconsistencies between studies however, limit our capacity to identify mechanisms for the developmental origin of these diseases in animal models of overnutrition.H Ainge, C Thompson, SE Ozanne and KB Roone

The discrimination ratio derived from novel object recognition tasks as a measure of recognition memory sensitivity, not bias

Translational recognition memory research makes frequent use of the Novel Object Recognition (NOR) paradigm in which animals are simultaneously presented with one new and one old object. The preferential exploration of the new as compared to the old object produces a metric, the Discrimination Ratio (DR), assumed to represent recognition memory sensitivity. Human recognition memory studies typically assess performance using signal detection theory derived measures; sensitivity (d′) and bias (c). How DR relates to d′ and c and whether they measure the same underlying cognitive mechanism is, however, unknown. We investigated the correspondence between DR (eye-tracking-determined), d′ and c in a sample of 37 humans. We used dwell times during a visual paired comparison task (analogous to the NOR) to determine DR, and a separate single item recognition task to derive estimates of response sensitivity and bias. DR was found to be significantly positively correlated to sensitivity but not bias. Our findings confirm that DR corresponds to d′, the primary measure of recognition memory sensitivity in humans, and appears not to reflect bias. These findings are the first of their kind to suggest that animal researchers should be confident in interpreting the DR as an analogue of recognition memory sensitivity