Bank voles show more impulsivity in IntelliCage learning tasks than wood mice

Impulsivity is a personality trait of healthy individuals, but in extreme forms common in mental disorders. Previous behavioral testing of wild-caught bank voles and wood mice suggested impulsiveness in bank voles. Here, we compared behavioral performance of bank voles and wood mice in tests for response control in the IntelliCage. In the reaction time task, a test similar to the five-choice serial-reaction time task (5CSRTT), bank voles made more premature responses. Impulsivity in the reaction time task was associated with smaller medial habenular nucleus in bank voles. Additional tests revealed reduced behavioral flexibility in the self-paced flexibility task in bank voles, but equal spatial and reversal learning in the chaining/reversal task in both species. Expression of immediate early gene Arc after behavioral testing was low in medial prefrontal cortex, but high in hypothalamic supraoptic and paraventricular nucleus in bank voles. Wood mice showed the opposite pattern. Numbers of Arc-positive cells in the dorsal hippocampus were higher in bank voles than wood mice. Due to continuous behavioral testing (24/7), associations between behavioral performance and Arc were rare. Corticosterone measurements at the end of experiments suggested that IntelliCage testing did not elicit a stress response in these wild rodents. In summary, habenular size differences and altered activation of brain areas after testing might indicate differently balanced activations of cortico-limbic and cortico-hypothalamic circuits in bank voles compared to wood mice. Behavioral performance of bank voles suggest that these rodents could be a natural animal model for investigating impulsive and perseverative behaviors

Early deprivation induces competitive subordinance in C57BL/6 male mice

Rodent models have been widely used to investigate the impact of early life stress on adult health and behavior. However, the social dimension has rarely been incorporated into the analysis due to methodological limitations. This study characterized the effects of neonatal social isolation (early deprivation, ED) on adult C57BL/6 mouse behavior in a social context using our recently developed behavioral test protocols for group-housed mice. During the first two postnatal weeks, half of the pups per dam were separated from their dam and littermates for 3. h per day (ED group). Post weaning, ED and control pups were electronically tagged and co-housed. At 12. weeks, the mixed cohorts were transferred to IntelliCages, equipped with computer-controlled operant chambers. Access to the chambers was used as an index to analyze novel object response, behavioral flexibility, and competitive dominance with minimal experimenter intervention. In general, ED had greater effects on males; ED males exhibited reduced body weight, increased novelty response, and were subordinate to control littermates when competing for reward access. Male ED mice also demonstrated mildly impaired reversal learning. Analyzing gene expression changes in brain regions controlling emotion, stress, spatial memory, and executive function revealed reduced BDNF and c-Fos in hippocampal CA1, enhanced c-Fos in the basolateral amygdala, reduced Map2 while enhanced HSD11β2 in prefrontal cortex of ED males. In male mice, it was suggested that neonatal social isolation results in sustained changes in social behavior with altered function of limbic and frontal cortices

IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system

IntelliCage for mice is a rodent home-cage equipped with four corner structures harboring symmetrical double panels for operant conditioning at each of the two sides, either by reward (access to water) or by aversion (non-painful stimuli: air-puffs, LED lights). Corner visits, nose-pokes and actual licks at bottle-nipples are recorded individually using subcutaneously implanted transponders for RFID identification of up to 16 adult mice housed in the same home-cage. This allows for recording individual in-cage activity of mice and applying reward/punishment operant conditioning schemes in corners using workflows designed on a versatile graphic user interface. IntelliCage development had four roots: (i) dissatisfaction with standard approaches for analyzing mouse behavior, including standardization and reproducibility issues, (ii) response to handling and housing animal welfare issues, (iii) the increasing number of mouse models had produced a high work burden on classic manual behavioral phenotyping of single mice. and (iv), studies of transponder-chipped mice in outdoor settings revealed clear genetic behavioral differences in mouse models corresponding to those observed by classic testing in the laboratory. The latter observations were important for the development of home-cage testing in social groups, because they contradicted the traditional belief that animals must be tested under social isolation to prevent disturbance by other group members. The use of IntelliCages reduced indeed the amount of classic testing remarkably, while its flexibility was proved in a wide range of applications worldwide including transcontinental parallel testing. Essentially, two lines of testing emerged: sophisticated analysis of spontaneous behavior in the IntelliCage for screening of new genetic models, and hypothesis testing in many fields of behavioral neuroscience. Upcoming developments of the IntelliCage aim at improved stimulus presentation in the learning corners and videotracking of social interactions within the IntelliCage. Its main advantages are (i) that mice live in social context and are not stressfully handled for experiments, (ii) that studies are not restricted in time and can run in absence of humans, (iii) that it increases reproducibility of behavioral phenotyping worldwide, and (iv) that the industrial standardization of the cage permits retrospective data analysis with new statistical tools even after many years

Bank Voles Show More Impulsivity in IntelliCage Learning Tasks than Wood Mice

Impulsivity is a personality trait of healthy individuals, but in extreme forms common in mental disorders. Previous behavioral testing of wild-caught bank voles and wood mice suggested impulsiveness in bank voles. Here, we compared behavioral performance of bank voles and wood mice in tests for response control in the IntelliCage. In the reaction time task, a test similar to the five-choice serial-reaction time task (5CSRTT), bank voles made more premature responses. Impulsivity in the reaction time task was associated with smaller medial habenular nucleus in bank voles. Additional tests revealed reduced behavioral flexibility in the self-paced flexibility task in bank voles, but equal spatial and reversal learning in the chaining/reversal task in both species. Expression of immediate early gene Arc after behavioral testing was low in medial prefrontal cortex, but high in hypothalamic supraoptic and paraventricular nucleus in bank voles. Wood mice showed the opposite pattern. Numbers of Arc-positive cells in the dorsal hippocampus were higher in bank voles than wood mice. Due to continuous behavioral testing (24/7), associations between behavioral performance and Arc were rare. Corticosterone measurements at the end of experiments suggested that IntelliCage testing did not elicit a stress response in these wild rodents. In summary, habenular size differences and altered activation of brain areas after testing might indicate differently balanced activations of cortico-limbic and cortico-hypothalamic circuits in bank voles compared to wood mice. Behavioral performance of bank voles suggest that these rodents could be a natural animal model for investigating impulsive and perseverative behaviors.ISSN:0306-4522ISSN:1873-754

Additional file: 1 of Application of NeuroTrace staining in the fresh frozen brain samples to laser microdissection combined with quantitative RT-PCR analysis

Figure S1. Visualization of neurons of ethanol-fixed and NeuroTrace-stained third ventricle (D3V) specimen under (A1) a bright field and (A2) a fluorescence radiated field. The staining of the choroid plexus is thought to be a non-specific signal commonly observed in fresh frozen samples stained with regular Nissl stains, such as Cresyl violet, and is often considered negligible as it is irrelevant to the cerebral parenchyma. (A3) Ethanol-fixed hippocampal CA1 region under a fluorescent light, left side with the NeuroTrace stain and right side without it. (B1) Ethanol-fixed and NeuroTrace-stained neurons of the hippocampal DG region (B2) before and (B3) after microdissection, indicated by red arrows. Scales bars: (A) 200 Îźm, (B1) 100 Îźm, and (B2, B3) 25 Îźm

Low uric acid levels in patients with Parkinson's disease: evidence from meta-analysis

Figure S5. Transcript levels of (A) 18S rRNA, (B) GAPDH, and (C) β-actin mRNAs in samples fixed with ethanol for 10 s, 30 s, and 60 s in comparison with the untreated samples. Values are expressed as copy number of transcripts per 182 nm2 × 20 μm cryosection thickness. Bars indicate mean ± SEM. One-way ANOVA followed by Tukey post hoc test, where **p < 0.01, ***p < 0.001. n = 7 for the untreated samples, n = 6 for 10 s fixation, and n = 8 for 30 s and 60 s fixation

Additional file: 3 of Application of NeuroTrace staining in the fresh frozen brain samples to laser microdissection combined with quantitative RT-PCR analysis

Figure S3. (A–C) Correlation of the transcript levels between the housekeeping genes in unfixed and unstained (Untreated; crosses) and ethanol and NeuroTrace-treated (EtOH/NT; circles) samples: (A) β-actin vs. 18S rRNA, (B) GAPDH vs. 18S rRNA, and (C) GAPDH vs. β-actin. (D–E) Correlation between the transcript levels of the housekeeping genes and Map2: (D) β-actin vs. Map2, (E) 18S rRNA vs. Map2, and (F) GAPDH vs. Map2. Values are expressed as copy number of transcripts per LMD tissue of 182 nm2 × cryosection thickness in volume. For untreated samples, n = 7 for 20 μm, n = 6 for 30 μm, and n = 8 for 40 μm; for fixed and stained samples, n = 7 for 20 μm, n = 7 for 30 μm, and n = 8 for 40 μm

Table_1_Associations between prefrontal PI (16:0/20:4) lipid, TNC mRNA, and APOA1 protein in schizophrenia: A trans-omics analysis in post-mortem brain.xlsx

BackgroundThough various mechanisms have been proposed for the pathophysiology of schizophrenia, the full extent of these mechanisms remains unclear, and little is known about the relationships among them. We carried out trans-omics analyses by comparing the results of the previously reported lipidomics, transcriptomics, and proteomics analyses; all of these studies used common post-mortem brain samples.MethodsWe collected the data from three aforementioned omics studies on 6 common post-mortem samples (3 schizophrenia patients and 3 controls), and analyzed them as a whole group sample. Three correlation analyses were performed for each of the two of three omics studies in these samples. In order to discuss the strength of the correlations in a limited sample size, the p-values of each correlation coefficient were confirmed using the Student’s t-test. In addition, partial correlation analysis was also performed for some correlations, to verify the strength of the impact of each factor on the correlations.ResultsThe following three factors were strongly correlated with each other: the lipid level of phosphatidylinositol (PI) (16:0/20:4), the amount of TNC mRNA, and the quantitative signal intensity of APOA1 protein. PI (16:0/20:4) and TNC showed a positive correlation, while PI (16:0/20:4) and APOA1, and TNC and APOA1 showed negative correlations. All of these correlations reached at p ConclusionThe current results suggest that these three factors may provide new clues to elucidate the relationships among the candidate mechanisms of schizophrenia, and support the potential of trans-omics analyses as a new analytical method.</p