É crescente o interesse nos efeitos que o ambiente parental exerce sobre o fenótipo da prole, a chamada herança epigenética. Tem sido mostrado que essa herança ocorre especialmente para efeitos de plasticidade do desenvolvimento, os quais derivam de alteração ambiental durante o desenvolvimento parental. Dentre os estudados realizados em camundongos, várias estratégias ambientais foram abordadas, como o estresse durante a infância e o enriquecimento ambiental, com a avaliação da prole em relação a parâmetros comportamentais, fisiológicos e moleculares. De modo a estudar o fenômeno, o presente trabalho investigou, em camundongos Swiss machos, os efeitos de um estresse durante a infância, a Privação Materna em PND 9, com avaliação de comportamentos exploratório (Campo Aberto), do tipo ansioso (Labirinto em Cruz Elevado), depressivo (Nado Forçado) e relacionados ao álcool (Condicionamento Condicionado por Lugar e Sensibilização Comportamental), e, numa outra abordagem, do Enriquecimento Ambiental do desmame (PND 21) à idade adulta (PND 70), com avaliação de parâmetros fisiológicos diversos (peso corporal, de depósito de gordura, de baço e glândulas adrenais) e comportamentos exploratório (Campo Aberto), memória espacial (Labirinto de Barnes), dominância social (Tubo de Dominância Social), atratividade (Teste de Escolha de Parceiro), além de avaliação de corticosterona plasmática e BDNF hipocampal. A privação materna não promoveu diferenças para os parâmetros comportamentais avaliados. Optou-se pela utilização do paradigma do Enriquecimento Ambiental para investigação dos efeitos sobre o fenótipo da prole (machos e fêmeas). Foram observados nos filhotes machos resultados comportamentais opostos aos apresentados pela geração paterna. Porém, quando os filhos foram expostos a um período breve de enriquecimento durante a idade adulta, essas diferenças não foram mais encontradas. Portanto, conclui-se que o enriquecimento ambiental paterno foi capaz de gerar efeitos na prole, tornando os filhotes machos menos adaptados ao ambiente não enriquecido. / There is a growing interest in the effects of the parental environment on the offspring phenotype, the so-called epigenetic inheritance. It has been shown that this inheritance occurs especially for developmental plasticity effects, which stem from environmental changes during parental development. Studies carried out in mice have adopted several environmental strategies, such as early life stress and environmental enrichment, and the offspring have been assessed for behavioural, physiological and molecular parameters. In order to study the phenomenon, the present work investigated, in Swiss male mice, the effects of an early-life stress protocol, the Maternal Deprivation on PND 9, assessing behaviours such as exploratory (Open Field), anxiety-like (Elevated-Plus Maze), depressive-like (Forced Swim) and alcohol-related behaviours (Conditioned Place Preference and Behavioural Sensitisation) and, through a different approach, the environmental enrichment, from weaning (PND 21) to adulthood (PND 70), assessing diverse physiological parameters (body weight, fat pad weight, spleen and adrenal glands weights) and behaviours such as exploratory (Open Field), spatial memory (Barnes Maze), social dominance (Social Dominance Tube Test), attractiveness (Mate Choice Teste) as well as plasmatic corticosterone and hippocampal BDNF. The maternal deprivation did not yield any differences in the behavioural parameters assessed. The Environmental Enrichment paradigm was adopted for studying its effects on the offspring phenotype (males and females). Behavioural results were observed in the male offspring, which were the opposite of those found in the paternal generation. However, when the male offspring was exposed to a brief period of enrichment during adulthood, these differences were no longer found. Therefore, paternal environmental enrichment was able to induce effects on the offspring, turning male offspring less adapted to the non-enriched environment.

Knowledge about the configuration of an environment is used preferentially when navigating through an urban environment (Penn, 2003). However, it the locus of this effect is poorly understood. One possibility is that the local environment, such as the shape of an intersection, is sufficient to determine route choice in the context of the global configuration of an environment (Meilinger, Franz, & Bülthoff, in press; Meilinger, Knauff & Bülthoff, 2008). Two experiments were performed to investigate this hypothesis using two novel virtual environments, one with a simplistic configuration, and one with a more complicated configuration. In Experiment 1, peripheral vision was either available or constrained throughout a wayfinding task. A significant influence of global configuration information with minimal use of local configuration account was found. In Experiment 2, central vision was either limited to the local intersection or unconstrained. Again, a strong effect of configuration was found, with limited evidence for the use of local visual information. The results support a synergistic mechanism of wayfinding where the environmental configuration is used to inform existing knowledge about the environment.

Knowledge about the configuration of an environment is used preferentially when navigating through an urban environment (Penn, 2003). However, it the locus of this effect is poorly understood. One possibility is that the local environment, such as the shape of an intersection, is sufficient to determine route choice in the context of the global configuration of an environment (Meilinger, Franz, & Bülthoff, in press; Meilinger, Knauff & Bülthoff, 2008). Two experiments were performed to investigate this hypothesis using two novel virtual environments, one with a simplistic configuration, and one with a more complicated configuration. In Experiment 1, peripheral vision was either available or constrained throughout a wayfinding task. A significant influence of global configuration information with minimal use of local configuration account was found. In Experiment 2, central vision was either limited to the local intersection or unconstrained. Again, a strong effect of configuration was found, with limited evidence for the use of local visual information. The results support a synergistic mechanism of wayfinding where the environmental configuration is used to inform existing knowledge about the environment.

With the rapid advancements in technology, researchers are seeking new ways to incorporate modern high-tech solutions such as virtual reality into treatment paradigms for stress. The current experiment explores the beneficial effects of immersing an individual into virtual reality after a stressful encounter. I examined the potential restorative effects of three unique immersive virtual reality environments by inducing stress and negative affect in sixty-nine participants and then randomly assigning them to freely explore one of three environments (a virtual nature setting, a virtual urban cityscape, or a neutral environment composed of solid geometric shapes) for ten minutes. Participants who explored the nature environment were found to have significantly improved affect (as measured by a standardized questionnaire), and significantly lower stress levels (as measured by self-report and skin-conductance levels) compared to those who explored the urban and geometric environments. The results suggest that virtual nature has restorative properties similar to real nature, and that simply immersing participants into a virtual nature setting can reduce stress. These results also suggest that the content of the virtual reality experience (i.e., whether it contains nature) is important in promoting restoration, and that in the absence of nature, stress levels remain unchanged.

The ability to correct balance disturbances is essential for maintaining upright stability. Recent literature highlights a potentially important role for the cerebral cortex in controlling compensatory balance reactions. The objective of this research was to provide a more detailed understanding of the specific neurophysiologic events occurring at the cortex following balance disturbances. More specifically, the focus was to determine whether the N1, a cortical potential evoked during balance control, and the error-related negativity (ERN), a cortical potential measured in response to errors during cognitive tasks, have similar cortical representation, revealing a similar link to an error detection mechanism. It was hypothesized that the N1 and ERN would have the same generator located in the anterior cingulate cortex (ACC). Fourteen healthy young adults participated in a balance task (evoked N1) and a flanker task (evoked ERN). Temporally unpredictable perturbations to standing balance were achieved using a lean and release cable system. Electromyography and centre of pressure were measured during the balance task. Reaction times and error rates were measured during the flanker task. Electroencephalography was recorded during both tasks. Source localization was performed in CURRY 6 using a single fixed coherent dipole model to determine the neural generator of the N1 and ERN. The results revealed that the locations of the N1 and ERN dipoles were different. The mean (n=9) distance between N1 and ERN dipoles was 25.46 ± 8.88 mm. The mean Talairach coordinates for the ERN dipole were (6.47 ± 3.08, -4.41 ± 13.15, 41.17 ± 11.63) mm, corresponding to the cingulate gyrus (Brodmann area 24). This represents the ACC, supporting results from previous literature. The mean Talairach coordinates for the N1 dipole were (5.74 ± 3.77, -11.81 ± 10.84, 53.73 ± 7.30) mm, corresponding to the medial frontal gyrus (Brodmann area 6). This is the first work to localize the source of the N1. It is speculated that the generator of the N1 is the supplementary motor area and that it represents the generation of a contingency motor plan to shape the later phases of the compensatory balance response based on sensory feedback from the perturbation.

With the rapid advancements in technology, researchers are seeking new ways to incorporate modern high-tech solutions such as virtual reality into treatment paradigms for stress. The current experiment explores the beneficial effects of immersing an individual into virtual reality after a stressful encounter. I examined the potential restorative effects of three unique immersive virtual reality environments by inducing stress and negative affect in sixty-nine participants and then randomly assigning them to freely explore one of three environments (a virtual nature setting, a virtual urban cityscape, or a neutral environment composed of solid geometric shapes) for ten minutes. Participants who explored the nature environment were found to have significantly improved affect (as measured by a standardized questionnaire), and significantly lower stress levels (as measured by self-report and skin-conductance levels) compared to those who explored the urban and geometric environments. The results suggest that virtual nature has restorative properties similar to real nature, and that simply immersing participants into a virtual nature setting can reduce stress. These results also suggest that the content of the virtual reality experience (i.e., whether it contains nature) is important in promoting restoration, and that in the absence of nature, stress levels remain unchanged.

The ability to correct balance disturbances is essential for maintaining upright stability. Recent literature highlights a potentially important role for the cerebral cortex in controlling compensatory balance reactions. The objective of this research was to provide a more detailed understanding of the specific neurophysiologic events occurring at the cortex following balance disturbances. More specifically, the focus was to determine whether the N1, a cortical potential evoked during balance control, and the error-related negativity (ERN), a cortical potential measured in response to errors during cognitive tasks, have similar cortical representation, revealing a similar link to an error detection mechanism. It was hypothesized that the N1 and ERN would have the same generator located in the anterior cingulate cortex (ACC). Fourteen healthy young adults participated in a balance task (evoked N1) and a flanker task (evoked ERN). Temporally unpredictable perturbations to standing balance were achieved using a lean and release cable system. Electromyography and centre of pressure were measured during the balance task. Reaction times and error rates were measured during the flanker task. Electroencephalography was recorded during both tasks. Source localization was performed in CURRY 6 using a single fixed coherent dipole model to determine the neural generator of the N1 and ERN. The results revealed that the locations of the N1 and ERN dipoles were different. The mean (n=9) distance between N1 and ERN dipoles was 25.46 ± 8.88 mm. The mean Talairach coordinates for the ERN dipole were (6.47 ± 3.08, -4.41 ± 13.15, 41.17 ± 11.63) mm, corresponding to the cingulate gyrus (Brodmann area 24). This represents the ACC, supporting results from previous literature. The mean Talairach coordinates for the N1 dipole were (5.74 ± 3.77, -11.81 ± 10.84, 53.73 ± 7.30) mm, corresponding to the medial frontal gyrus (Brodmann area 6). This is the first work to localize the source of the N1. It is speculated that the generator of the N1 is the supplementary motor area and that it represents the generation of a contingency motor plan to shape the later phases of the compensatory balance response based on sensory feedback from the perturbation.

Amyloid beta (ABeta) and tau protein are both implicated in memory impairment in early Alzheimer’s disease, but whether and how they interact to cause synaptic dysfunction are unknown. Consequently, I firstly investigated whether tau protein is required for the robust phenomenon of ABeta-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. I demonstrate that the absence of tau prevents the ABeta-induced impairment of LTP; moreover, a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks both an ABeta-induced increase in tau phosphorylation and the ABeta-induced LTP impairment. Thus, tau protein, likely in its phosphorylated form, is required for ABeta to impair LTP. Secondly, I investigated the underlying mechanisms for this ABeta-induced impairment and find that ABeta changes the balance between the two major types of glutamate receptors involved in plasticity processes, with a specific effect on GluN2B subunit-containing NMDA receptors. Since the distribution of these receptors is asymmetric between the left and right mouse hippocampus, I accessed these different types of synapses optogenetically and found that only the GluN2B-rich synapses receiving left CA3 input show ABeta-induced changes in the balance of glutamate receptors, suggesting an asymmetry in synaptic vulnerability to ABeta. Moreover, there was a left-right difference in tetanus-induced LTP and therefore, thirdly, I investigated whether mice have a hemispheric dissociation in memory processing using acute optogenetic silencing of left or right CA3 during hippocampus-dependent memory tasks. Unilateral silencing of either the left or the right CA3 caused a deficit in short-term memory, but only left CA3 silencing impaired performance on a spatial long-term memory task. Together, these results suggest that memory may be routed via distinct left-right pathways within the mouse hippocampus, and that neural pathways subserving distinct functions may also be differentially vulnerable to pathological changes at the synaptic level.

<p>A C. elegans model of nicotine use and aversion resistance following chronic low-dose nicotine pretreatment. Model was then applied to various receptor knockouts  (acr-5, acr-15, acr-16, dop-1, and dop-2) to determine the role of these receptors in aversion resistance. </p>

<p dir="ltr">Frontloading is an alcohol drinking pattern where intake is skewed toward the onset of access. The goal of the current study was to identify brain regions involved in frontloading using whole brain imaging. 63 C57Bl/6J (32 female and 31 male) mice underwent 8 days of binge drinking using drinking-in-the-dark (DID). Three hours into the dark cycle, mice received 20% (v/v) alcohol or water for two hours on days 1-7. Intake was measured in 1-minute bins using volumetric sippers, which facilitated analyses of drinking patterns. Mice were perfused 80 minutes into the day 8 DID session and brains were extracted and processed for iDISCO clearing and c-fos immunohistochemistry. For brain network analyses, day 8 drinking patterns were used to characterize mice as frontloaders or non-frontloaders using a change-point analysis described in our recent ACER publication (Ardinger et al., 2022). Groups were female frontloaders (n = 20), female non-frontloaders (n = 2), male frontloaders (n = 13) and male non-frontloaders (n = 8). There were no differences in total alcohol intake as a function of frontloading status. Water drinkers had an n of 10 for each sex. As only two female mice were characterized as non-frontloaders, it was not possible to construct a functional correlation network for this group. Following light sheet imaging, ClearMap2.1 was used to register brains to the Allen Brain Atlas and detect fos+ cells. Functional correlation matrices were calculated for each group from log₁₀ c-fos values. Euclidean distances were calculated from these R values and hierarchical clustering was used to determine modules (highly connected groups of brain regions) at a tree-cut height of 50%. In males, alcohol access decreased modularity (3 modules in both frontloaders and non-frontloaders) as compared to water drinkers (7 modules). In females, an opposite effect was observed. Alcohol access (9 modules) increased modularity as compared to water drinkers (5 modules). These results suggest sex differences in how alcohol consumption reorganizes the functional architecture of networks. Next, key brain regions in each network were identified. Connector hubs, which primarily facilitate communication between modules, and provincial hubs, which facilitate communication within modules, were of specific interest for their important and differing roles. In males, 4 connector hubs and 17 provincial hubs were uniquely identified in frontloaders (i.e., were brain regions that did not have this status in male non-frontloaders or water drinkers). These represented a group of hindbrain regions (e.g., locus coeruleus and the pontine gray) connected to striatal/cortical regions (e.g., cortical amygdalar area) by the paraventricular nucleus of the thalamus. In females, 16 connector and 17 provincial hubs were uniquely identified which were distributed across 8 of the 9 modules in the female alcohol drinker network. Only one brain region (the nucleus raphe pontis) was a connector hub in both sexes, suggesting that frontloading in males and females may be driven by different brain regions. In conclusion, alcohol consumption led to fewer, but more densely connected, groups of brain regions in males but not females, and recruited different hub brain regions between the sexes. These results suggest target brain regions for future studies to try to manipulate frontloading behavior and more broadly contribute to the literature on alcohol’s effect on neural networks.</p>