TY - JOUR AB - The formation of semantic memories is assumed to result from the abstraction of general, schema-like knowledge across multiple experiences, while at the same time, episodic details from individual experiences are forgotten. Against this backdrop, our study examined the effects of information load (high vs. low) during encoding on the formation of episodic and schema memory using an elaborated version of an object-place recognition (OPR) task in rats. The task allowed for the abstraction of a spatial rule across four (low information load) or eight (high information load) encoding episodes (spaced apart by a 20 min interval) in which the rats could freely explore two objects in an open field arena. After this encoding phase, animals were left undisturbed for 24 h and then tested either for the expression of schema memory, i.e., for the spatial rule, or memory for an individual encoding episode. Rats in the high information load condition exhibited a more robust schema memory for the spatial rule than in the low information load condition. In contrast, rats in the low load condition showed more robust memory for individual learning episodes than in the high information load condition. Our findings of opposing effects might point to an information-load-dependent competitive relationship between processes of schema and episodic memory formation, although other explanations are possible. AU - Harkotte, M.* AU - Contreras, M.P.* AU - Inostroza, M.* AU - Born, J. C1 - 65804 C2 - 52915 TI - Effects of information load on schema and episodic memory formation. JO - Front. Behav. Neurosci. VL - 16 PY - 2022 SN - 1662-5153 ER - TY - JOUR AB - Prenatal alcohol exposure (PAE) is known to elicit a broad range of systemic effects, including neurophysiological alterations that result in adverse behavioral and cognitive outcomes. However, molecular pathways underlying these long-term intrauterine effects remain to be investigated. Here, we tested a hypothesis that PAE may lead to epigenetic alterations to the DNA resulting in attentional and cognitive alterations of the children. We report the results of the study that included 156 primary school children of the Franconian Cognition and Emotion Studies (FRANCES) cohort which were tested for an objective marker of PAE, ethyl glucuronide (EtG) in meconium at birth. Thirty-two newborns were found to be exposed to alcohol with EtG values above 30 ng/g (EtG+). Previously we described PAE being associated with lower IQ and smaller amplitude of the event-related potential component P3 in go trials (Go-P3), which indicates a reduced capacity of attentional resources. Whole-genome methylation analysis of the buccal cell DNA revealed 193 differentially methylated genes in children with positive meconium EtG, that were clustered into groups involved in epigenetic modifications, neurodegeneration, neurodevelopment, axon guidance and neuronal excitability. Furthermore, we detected mediation effects of the methylation changes in and genes on the EtG related cognitive and attention-related deficits. Our results suggest that system-wide epigenetic changes are involved in long-term effects of PAE. In particular, we show an epigenetic mediation of PAE effects on cognition and attention-related processes. AU - Frey, S.* AU - Eichler, A.* AU - Stonawski, V.* AU - Kriebel, J. AU - Wahl, S. AU - Gallati, S.* AU - Goecke, T.W.* AU - Fasching, P.A.* AU - Beckmann, M.W.* AU - Kratz, O.* AU - Moll, G.H.* AU - Heinrich, H.* AU - Kornhuber, J.* AU - Golub, Y.* C1 - 53923 C2 - 45093 TI - Prenatal alcohol exposure is associated with adverse cognitive effects and distinct whole-genome DNA methylation patterns in primary school children. JO - Front. Behav. Neurosci. VL - 12 PY - 2018 SN - 1662-5153 ER - TY - JOUR AB - Operant extinction is learning to supress a previously rewarded behavior. It is known to be strongly associated with the specific context in which it was acquired, which limits the therapeutic use of operant extinction in behavioral treatments, e. g., of addiction. We examined whether sleep influences contextual memory of operant extinction over time, using two different recall tests (Recent and Remote). Rats were trained in an operant conditioning task (lever press) in context A, then underwent extinction training in context B, followed by a 3-h retention period that contained either spontaneous morning sleep, morning sleep deprivation, or spontaneous evening wakefulness. A recall test was performed either immediately after the 3-h experimental retention period (Recent recall) or after 48 h (Remote), in the extinction context B and in a novel context C. The two main findings were: (i) at the Recent recall test, sleep in comparison with sleep deprivation and spontaneous wakefulness enhanced extinction memory but, only in the extinction context B; (ii) at the Remote recall, extinction performance after sleep was enhanced in both contexts B and C to an extent comparable to levels at Recent recall in context B. Interestingly, extinction performance at Remote recall was also improved in the sleep deprivation groups in both contexts, with no difference to performance in the sleep group. Our results suggest that 3 h of post-learning sleep transiently facilitate the context specificity of operant extinction at a Recent recall. However, the improvement and contextual generalization of operant extinction memory observed in the long-term, i. e., after 48 h, does not require immediate post-learning sleep. AU - Borquez, M.* AU - Contreras, M.P.* AU - Vivaldi, E.* AU - Born, J. AU - Inostroza, M.* C1 - 51134 C2 - 42921 CY - Lausanne TI - Post-learning sleep transiently boosts context specific operant extinction memory. JO - Front. Behav. Neurosci. VL - 11 PB - Frontiers Media Sa PY - 2017 SN - 1662-5153 ER - TY - JOUR AB - Social memory refers to the fundamental ability of social species to recognize their conspecifics in quite different contexts. Sleep has been shown to benefit consolidation, especially of hippocampus-dependent episodic memory whereas effects of sleep on social memory are less well studied. Here, we examined the effect of sleep on memory for conspecifics in rats. To discriminate interactions between the consolidation of social memory and of spatial context during sleep, adult Long Evans rats performed on a social discrimination task in a radial arm maze. The Learning phase comprised three 10-min sampling sessions in which the rats explored a juvenile rat presented at a different arm of the maze in each session. Then the rats were allowed to sleep (n = 18) or stayed awake (n = 18) for 120 min. During the following 10-min Test phase, the familiar juvenile rat (of the Learning phase) was presented along with a novel juvenile rat, each rat at an opposite arm of the maze. Significant social recognition memory, as indicated by preferential exploration of the novel over the familiar conspecific, occurred only after post-learning sleep, but not after wakefulness. Sleep, compared with wakefulness, significantly enhanced social recognition during the first minute of the Test phase. However, memory expression depended on the spatial configuration: Significant social recognition memory emerged only after sleep when the rat encountered the novel conspecific at a place different from that of the familiar juvenile in the last sampling session before sleep. Though unspecific retrieval-related effects cannot entirely be excluded, our findings suggest that sleep, rather than independently enhancing social and spatial aspects of memory, consolidates social memory by acting on an episodic representation that binds the memory of the conspecific together with the spatial context in which it was recently encountered. AU - Sawangjit, A.* AU - Kelemen, E.* AU - Born, J. AU - Inostroza, M.* C1 - 50678 C2 - 42829 CY - Lausanne TI - Sleep enhances recognition memory for conspecifics as bound into spatial context. JO - Front. Behav. Neurosci. VL - 11 PB - Frontiers Media Sa PY - 2017 SN - 1662-5153 ER - TY - JOUR AB - Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ) along the walls of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB)- and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreERT2 under doublecortin (DCX) promoter control were crossed with mice where diphtheria toxin A (DTA) was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM), results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months) and middle aged (from 10 months) mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the TAM treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior. AU - Garrett, L. AU - Zhang, J. AU - Zimprich, A. AU - Niedermeier, K.M. AU - Fuchs, H. AU - Gailus-Durner, V. AU - Hrabě de Angelis, M. AU - Vogt Weisenhorn, D.M. AU - Wurst, W. AU - Hölter, S.M. C1 - 47449 C2 - 40524 CY - Lausanne TI - Conditional reduction of adult born doublecortin-positive neurons reversibly impairs selective behaviors. JO - Front. Behav. Neurosci. VL - 9 PB - Frontiers Media Sa PY - 2015 SN - 1662-5153 ER - TY - JOUR AB - Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated and phenotyped in a large-scale manner, it seems advisable also to test these mutants for alterations in their stress responses. Here we present the determinants of a robust and reliable non-invasive test for stress-responsivity in mice. Stress is applied through restraining the mice in tubes and recording behavior in the Open Field 20 min after cessation of the stress. Two hours, but not 15 or 50 min of restraint lead to a robust and reproducible increase in distance traveled and number of rearings during the first 5 min in the Open Field in C57BL/6 mice. This behavioral response is blocked by the corticosterone synthesis inhibitor metyrapone, but not by RU486 treatment, indicating that it depends on corticosteroid secretion, but is not mediated via the glucocorticoid receptor type II. We assumed that with a stress duration of 15 min one could detect hyper-responsivity, and with a stress duration of 2 h hypo-responsivity in mutant mouse lines. This was validated with two mutant lines known to show opposing effects on corticosterone secretion after stress exposure, corticotropin-releasing hormone (CRH) over-expressing mice and CRH receptor 1 knockout (KO) mice. Both lines showed the expected phenotype, i.e., increased stress responsivity in the CRH over-expressing mouse line (after 15 min restraint stress) and decreased stress responsivity in the CRHR1-KO mouse line (after 2 h of restraint stress). It is possible to repeat the acute stress test several times without the stressed animal adapting to it, and the behavioral response can be robustly evoked at different ages, in both sexes and in different mouse strains. Thus, locomotor and rearing behavior in the Open Field after an acute stress challenge can be used as reliable, non-invasive indicators of stress responsivity and corticosterone secretion in mice. AU - Zimprich, A. AU - Garett, L. AU - Deussing, J.M. AU - Wotjak, C.T.* AU - Fuchs, H. AU - Gailus-Durner, V. AU - Hrabě de Angelis, M. AU - Wurst, W. AU - Hölter, S.M. C1 - 31201 C2 - 34289 CY - Lausanne TI - A robust and reliable non-invasive test for stress responsivity in mice. JO - Front. Behav. Neurosci. VL - 8 PB - Frontiers Research Foundation PY - 2014 SN - 1662-5153 ER -