Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

The processes of memory reconsolidation and extinction have received increasing attention in recent experimental research, as their potential clinical applications begin to be uncovered. A number of studies suggest that amnestic drugs injected after reexposure to a learning context can disrupt either of the two processes, depending on the behavioral protocol employed. Hypothesizing that reconsolidation represents updating of a memory trace in the hippocampus, while extinction represents formation of a new trace, we have built a neural network model in which either simple retrieval, reconsolidation or extinction of a stored attractor can occur upon contextual reexposure, depending on the similarity between the representations of the original learning and reexposure sessions. This is achieved by assuming that independent mechanisms mediate Hebbian-like synaptic strengthening and mismatch-driven labilization of synaptic changes, with protein synthesis inhibition preferentially affecting the former. Our framework provides a unified mechanistic explanation for experimental data showing (a) the effect of reexposure duration on the occurrence of reconsolidation or extinction and (b) the requirement of memory updating during reexposure to drive reconsolidation

Multiple spine boutons are formed after long-lasting LTP in the awake rat

The formation of multiple spine boutons (MSBs) has been associated with cognitive abilities including hippocampal-dependent associative learning and memory. Data obtained from cultured hippocampal slices suggest that the long-term maintenance of synaptic plasticity requires the formation of new synaptic contacts on pre-existing synapses. This postulate however, has never been tested in the awake, freely moving animals. In the current study, we induced long-term potentiation (LTP) in the dentate gyrus (DG) of awake adult rats and performed 3-D reconstructions of electron micrographs from thin sections of both axonal boutons and dendritic spines, 24 h post-induction. The specificity of the observed changes was demonstrated by comparison with animals in which long-term depression (LTD) had been induced, or with animals in which LTP was blocked by an N-methyl-D-aspartate (NMDA) antagonist. Our data demonstrate that whilst the number of boutons remains unchanged, there is a marked increase in the number of synapses per bouton 24 h after the induction of LTP. Further, we demonstrate that this increase is specific to mushroom spines and not attributable to their division. The present investigation thus fills the gap existing between behavioural and in vitro studies on the role of MSB formation in synaptic plasticity and cognitive abilities

“Everything is not

There is ample evidence that macroscopic animals form geographic clusters termed as zoogeographic realms, whereas distributions of species of microscopic animals are still poorly understood. The common view has been that micrometazoans, thanks to their putatively excellent dispersal abilities, are subject to the “Everything is everywhere but environment selects” hypothesis (EiE). One of such groups, <1 mm in length, are limnoterrestrial water bears (Tardigrada), which can additionally enter cryptobiosis that should further enhance their potential for long distance dispersion (e.g., by wind). However, an increasing number of studies, including the most recent phylogeny of the eutardigrade genus Milnesium, seem to question the general applicability of the EiE hypothesis to tardigrade species. Nevertheless, all Milnesium phylogenies published to date were based on a limited number of populations, which are likely to falsely suggest limited geographic ranges. Thus, in order to test the EiE hypothesis more confidently, we considerably enlarged the Milnesium d ata s et b oth t axonomically and geographically, and analysed it in tandem with climate type and reproductive mode. Additionally, we time-calibrated our phylogeny to align it with major geological events. Our results show that, although cases of long distance dispersal are present, they seem to be rare and mostly ancient. Overall, Milnesium species are restricted to single zoogeographic realms, which suggests that these tardigrades have limited dispersal abilities. Finally, our results also suggest that the breakdown of Gondwana may have influenced the evolutionary history of Milnesium. In conclusion, phylogenetic relationships within the genus seem to be determined mainly by paleogeography