Cellular Correlates of Enhanced Anxiety Caused by Acute Treatment with the Selective Serotonin Reuptake Inhibitor Fluoxetine in Rats

Selective serotonin reuptake inhibitors (SSRIs) are used extensively in the treatment of depression and anxiety disorders. The therapeutic benefits of SSRIs typically require several weeks of continuous treatment. Intriguingly, according to clinical reports, symptoms of anxiety may actually increase during the early stages of treatment although more prolonged treatment alleviates affective symptoms. Consistent with earlier studies that have used animal models to capture this paradoxical effect of SSRIs, we find that rats exhibit enhanced anxiety-like behavior on the elevated plus-maze 1 h after a single injection of the SSRI fluoxetine. Next we investigated the potential neural substrates underlying the acute anxiogenic effects by analyzing the morphological and physiological impact of acute fluoxetine treatment on principal neurons of the basolateral amygdala (BLA), a brain area that plays a pivotal role in fear and anxiety. Although earlier studies have shown that behavioral or genetic perturbations that are anxiogenic for rodents also increase dendritic spine density in the BLA, we find that a single injection of fluoxetine does not cause spinogenesis on proximal apical dendritic segments on BLA principal neurons an hour later. However, at the same time point when a single dose of fluoxetine caused enhanced anxiety, it also enhanced action potential firing in BLA neurons in ex vivo slices. Consistent with this finding, in vitro bath application of fluoxetine caused higher spiking frequency and this increase in excitability was correlated with an increase in the input resistance of these neurons. Our results suggest that enhanced excitability of amygdala neurons may contribute to the increase in anxiety-like behavior observed following acute fluoxetine treatment

Early life stress determines the effects of glucocorticoids and stress on hippocampal function:Electrophysiological and behavioral evidence respectively

Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and post synaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. (C) 2018 Published by Elsevier Ltd

Dendritic Morphology of Hippocampal and Amygdalar Neurons in Adolescent Mice Is Resilient to Genetic Differences in Stress Reactivity

Many studies have shown that chronic stress or corticosterone over-exposure in rodents leads to extensive dendritic remodeling, particularly of principal neurons in the CA3 hippocampal area and the basolateral amygdala. We here investigated to what extent genetic predisposition of mice to high versus low stress reactivity, achieved through selective breeding of CD-1 mice, is also associated with structural plasticity in Golgi-stained neurons. Earlier, it was shown that the highly stress reactive (HR) compared to the intermediate (IR) and low (LR) stress reactive mice line presents a phenotype, with respect to neuroendocrine parameters, sleep architecture, emotional behavior and cognition, that recapitulates some of the features observed in patients suffering from major depression. In late adolescent males of the HR, IR, and LR mouse lines, we observed no significant differences in total dendritic length, number of branch points and branch tips, summated tip order, number of primary dendrites or dendritic complexity of either CA3 pyramidal neurons (apical as well as basal dendrites) or principal neurons in the basolateral amygdala. Apical dendrites of CA1 pyramidal neurons were also unaffected by the differences in stress reactivity of the animals; marginally higher length and complexity of the basal dendrites were found in LR compared to IR but not HR mice. In the same CA1 pyramidal neurons, spine density of distal apical tertiary dendrites was significantly higher in LR compared to IR or HR animals. We tentatively conclude that the dendritic complexity of principal hippocampal and amygdala neurons is remarkably stable in the light of a genetic predisposition to high versus low stress reactivity, while spine density seems more plastic. The latter possibly contributes to the behavioral phenotype of LR versus HR animals

ANALISIS FAKTOR – FAKTOR YANG MEMPENGARUHI PERAN PRODUKTIF WANITA RUMAH TANGGA NELAYAN DI KOTA BENGKULU

The aims of this study were (1) to analyze the decision making pattern towards productive role aspects of the fisheries households women in Bengkulu City (2) to analyze the push factors that affect the productive role decision making of fisheries households women in Bengkulu City (3) to analyze the pull factors that affect the productive role decision making of fisheries households women in Bengkulu City (4) to analyze the pattern of productive role decision making of fisheries households women in Bengkulu City, based on the push and pull factors. There are 100 fisheries households women in Bengkulu City were selected with a simple random sampling method. Techniques of data analysis used qualitative descriptive and Multinomial Logit Regression. The result showed that productive role decision making mostly decided by women herself (wife only), with the percentages of encouragement to do the productive role aspect (40%), type of job aspect (54%), work place aspect (59%), and work time aspect (60%). According to every aspects, women/wife also dominated (39%) of productive role decision making. Push factors that have significant effect to the productive role decision making are education (EDU) and working experience (WORK) factors. Pull factor that has significant effect to the productive role decision making is family support (D 1 ) factor. The analysis of push and pull factors acknowledged that women have higher domination, t han men i n wom en’ s pro ducti ve ro le de cision maki ng Keywords: Productive Role, Decision Making, Fisheries Households Women, Multinomial Logit Regressio

Bi-exponential fitting and pharmacological blockade of AHP responses in limbic pyramidal neurons.

<p><i>A</i>: AHP recording from a representative CA1 neuron (gray) and the fit (dark gray) overlaid with the extracted decay of the medium (black-dotted) and sAHP (black-continuous) recorded from the same neuron before and after Forskolin (50 µm, 15 min) application. Inset shows the current protocol used to evoke the AHPs. <i>B</i>: AHP recording from a representative layer 2/3 lateral OFC neuron before and after Forskolin treatment. <i>C</i>: The goodness of fit (R²) to the AHP response is averaged across CA1 neurons recorded from the vehicle (gray diamond) and corticosterone (black circles) groups. <i>D</i>: Goodness of fit to the AHP response from layer 2/3 lateral OFC neurons. <i>E</i>: Goodness of fit to the AHP response from layer 2/3 prelimbic neurons. <i>F</i>: Goodness of fit to the AHP response from layer 2/3 infralimbic neurons. Number within brackets in the legends indicates number of neurons.</p

The long lasting effects of corticosterone treatment on AHPs and action potential firing of layer 2/3 infralimbic pyramidal neurons.

<p><i>A</i>: <i>left</i>: a sample pyramidal neuron filled with fluorescent dye. Inset: zoomed image of the neuron (white arrow). Scale bar equals 20 microns. <i>Right</i>, locations of the recorded neurons on a pictorial coronal mouse brain section. <i>B</i>: representative AHP responses from vehicle and corticosterone groups overlaid with the fit. Light gray: raw trace, thick dark gray: fit, dotted line: mAHP decay, thin black line: sAHP decay. Inset shows the current protocol used to evoke the AHPs. <i>C</i>: traces of action potentials from neurons representative of the vehicle and corticosterone groups. Marking indicate the positions of spike amplitude, half-width and threshold measurements. <i>D</i>: mAHP peak amplitude averaged per group and per current step. <i>E</i>: averaged values of sAHP peak amplitude for each current injection step. <i>F</i>: accommodation index (% ratio of the interspike intervals of the last two spikes to the first two spikes) from vehicle and corticosterone groups. Number within brackets in the legends indicates number of neurons.</p

Active and passive properties of neurons within each of the limbic brain regions were not significantly different between treatment (vehicle and corticosterone) groups.

<p>Active and passive properties of neurons within each of the limbic brain regions were not significantly different between treatment (vehicle and corticosterone) groups.</p

Stress-induced alterations in large-scale functional networks of the rodent brain

Stress-related psychopathology is associated with altered functioning of large-scale brain networks. Animal research into chronic stress, one of the most prominent environmental risk factors for development of psychopathology, has revealed molecular and cellular mechanisms potentially contributing to human mental disease. However, so far, these studies have not addressed the system-level changes in extended brain networks, thought to critically contribute to mental disorders. We here tested the effects of chronic stress exposure (10. days immobilization) on the structural integrity and functional connectivity patterns in the brain, using high-resolution structural MRI, diffusion kurtosis imaging, and resting-state functional MRI, while confirming the expected changes in neuronal dendritic morphology using Golgi-staining. Stress effectiveness was confirmed by a significantly lower body weight and increased adrenal weight. In line with previous research, stressed animals displayed neuronal dendritic hypertrophy in the amygdala and hypotrophy in the hippocampal and medial prefrontal cortex. Using independent component analysis of resting-state fMRI data, we identified ten functional connectivity networks in the rodent brain. Chronic stress appeared to increase connectivity within the somatosensory, visual, and default mode networks. Moreover, chronic stress exposure was associated with an increased volume and diffusivity of the lateral ventricles, whereas no other volumetric changes were observed. This study shows that chronic stress exposure in rodents induces alterations in functional network connectivity strength which partly resemble those observed in stress-related psychopathology. Moreover, these functional consequences of stress seem to be more prominent than the effects on gross volumetric change, indicating their significance for future research

Apical dendrites of CA1 pyramidal neurons are similar between high, intermediate and low stress reactivity mice.

<p><b><i>A & D</i></b>, Sholl plots indicate the distribution of dendritic length (apical & basal) at increasing distance from the center of the cell body. <b><i>B, C, E & F</i></b>, average values of total dendritic bifurcations (mean±sem, n, <i>apical</i>, HR: 11±1, 34; IR: 12±1, 37; LR: 13±1, 27, <i>basal</i>: HR: 8±1; IR: 7±1; LR: 9±1) and complexity (mean±sem, <i>apical</i>, HR: 74980±11398; IR: 79977±15016; LR: 85358±15671, <i>basal</i>, HR: 10007±1795; IR: 6065±822; LR: 10796±1724), averaged across cells, were not statistically different between groups.</p