Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density.DOI: http://dx.doi.org/10.7554/eLife.13424.001

The amygdala is a heterogeneous brain structure implicated in processing of emotions and storing the emotional aspects of memories. Gene activity markers such as c-Fos have been shown to reflect both neuronal activation and neuronal plasticity. Herein, we analyze the expression patterns of gene activity markers in the amygdala in response to either behavioral training or treatment with drugs of abuse and then we confront the results with data on other approaches to internal complexity of the amygdala. c-Fos has been the most often studied in the amygdala, showing specific expression patterns in response to various treatments, most probably reflecting functional specializations among amygdala subdivisions. In the basolateral amygdala, c-Fos expression appears to be consistent with the proposed role of this nucleus in a plasticity of the current stimulus-value associations. Within the medial part of the central amygdala, c-Fos correlates with acquisition of alimentary/gustatory behaviors. On the other hand, in the lateral subdivision of the central amygdala, c-Fos expression relates to attention and vigilance. In the medial amygdala, c-Fos appears to be evoked by emotional novelty of the experimental situation. The data on the other major subdivisions of the amygdala are scarce. In conclusion, the studies on the gene activity markers, confronted with other approaches involving neuroanatomy, physiology, and the lesion method, have revealed novel aspects of the amygdala, especially pointing to functional heterogeneity of this brain region that does not fit very well into contemporarily active debate on serial versus parallel information processing within the amygdala.

Human studies indicate that high impulsivity, novelty seeking and anxiety predispose individuals to alcohol abuse. Unclear, however, is whether the same phenotypes can be observed in laboratory animals prone to uncontrolled alcohol drinking. To characterize a novelty-seeking trait, anxiety, impulsivity, compulsivity and the motivation for natural rewards in mice, numerous tests were performed in the automated IntelliCage learning system. The same mice then had extended access to alcohol for 70 days, followed by the evaluation of addiction-like behaviors, including (1) the motivation for alcohol in a progressive-ratio schedule of reinforcement; (2) persistent and compulsive alcohol seeking and taking during signaled 'no alcohol' periods and (3) when subjected to punishment; and (4) the intensity of relapse after alcohol withdrawal. Our data suggest that high levels of anxiety-related traits (i.e. low novelty seeking, low resistance to punishment and a high level of compulsive behaviors) and high impulsivity predict addiction-like alcohol drinking in mice. Future studies are, however, warranted to create a valid model of alcohol addiction in mice in the IntelliCage system.

One of the features of cellular senescence is the activity of senescenceassociated-β-galactosidase (SA-β-gal). The main purpose of this study was to evaluate this marker of senescence in aging neurons. We found that cortical neurons exhibited noticeable SA-β-gal activity quite early in culture. Many SA-β-gal-positive neurons were negative for another canonical marker of senescence, namely, doublestrand DNA breaks (DSBs). Moreover, DDR signalling triggered by low doses of doxorubicin did not accelerate the appearance of neuronal SA-β-gal. In vivo, we observed pronounced induction of SA-β-gal activity in the hippocampus of 24-monthold mice, which is consistent with previous findings and supports the view that at this advanced age neurons developed a senescence-like phenotype. Surprisingly however, relatively high SA-β-gal activity, probably unrelated to the senescence process, was also observed in much younger, 3-month-old mice. In conclusion, we propose that SA-β-gal activity in neurons cannot be attributed uniquely to cell senescence either in vitro or in vivo. Additionally, we showed induction of REST protein in aging neurons in long-term culture and we propose that REST could be a marker of neuronal senescence in vitro.