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

Temporal Discounting of Different Commodities in Airline Customer Reward Programs

Customer reward programs are commonly used by airlines in order to entice customers to collect points or miles. If customers engage in the reward program they are more likely to stay loyal to the airline and also purchase more trips. One problem with getting customers to engage in customer reward programs is that rewards that are going to be delivered at a future date tend to be less valuable to the customer than immediate rewards. This holds true even if the reward that would be received some time in the future is larger. Here we have determined if the rewards typically provided by airline customer reward programs, points, upgrades to first class travel or free trips are devalued over time. We also posed the question if these rewards are devalued at different rates over time. In addition, we investigated if the devaluing over time of different rewards is similar in different groups of customers defined by their age, location, income or gender. This was achieved by recruiting subjects by email to fill out a questionnaire containing questions that determining the value of different rewards at different time points using a fill-in-the-black method of measuring temporal discounting, as well as demographic information. Our results demonstrate that all three rewards investigated, points, upgrades and free trips, were less valuable when they were received at a later time point. Free trips were devalued the least over time in comparison to points and upgrades. Location, income and gender did not have a significant impact on how participants devalued the different types of rewards. However, age did affect how much upgrades were devalued over time, with the older groups (56-75) of participants devaluing the upgrades less over time than the younger groups (18-55)

Temporal Discounting of Different Commodities in Airline Customer Reward Programs

Customer reward programs are commonly used by airlines in order to entice customers to collect points or miles. If customers engage in the reward program they are more likely to stay loyal to the airline and also purchase more trips. One problem with getting customers to engage in customer reward programs is that rewards that are going to be delivered at a future date tend to be less valuable to the customer than immediate rewards. This holds true even if the reward that would be received some time in the future is larger. Here we have determined if the rewards typically provided by airline customer reward programs, points, upgrades to first class travel or free trips are devalued over time. We also posed the question if these rewards are devalued at different rates over time. In addition, we investigated if the devaluing over time of different rewards is similar in different groups of customers defined by their age, location, income or gender. This was achieved by recruiting subjects by email to fill out a questionnaire containing questions that determining the value of different rewards at different time points using a fill-in-the-black method of measuring temporal discounting, as well as demographic information. Our results demonstrate that all three rewards investigated, points, upgrades and free trips, were less valuable when they were received at a later time point. Free trips were devalued the least over time in comparison to points and upgrades. Location, income and gender did not have a significant impact on how participants devalued the different types of rewards. However, age did affect how much upgrades were devalued over time, with the older groups (56-75) of participants devaluing the upgrades less over time than the younger groups (18-55)

Antidepressant treatment differentially affects the phenotype of high and low stress reactive mice

Modelling key endophenotypes can be a powerful approach to gain insight into mechanisms underlying the aetiology and pathophysiology of neuropsychiatric disorders. Based on evidence of stress hormone system dysregulations in depression, the Stress Reactivity (SR) mouse model has been generated by a selective breeding approach for extremes in HPA axis reactivity, resulting in high (HR), intermediate (IR) and low (LR) reactive mice. The characterisation of their phenotypic alterations has highlighted many similarities of HR and LR mice with the melancholic and atypical depression, respectively. We therefore aimed to examine whether the antidepressant fluoxetine (10 mg/kg/day i.p., 4–5 weeks) can ameliorate the phenotypic characteristics of HR and LR mice in neuroendocrine functions (HPA axis basal activity, stress reactivity, negative feedback), emotional reactivity/coping-strategy (open field, forced swim tests), spatial learning/memory (Morris water-maze) and hippocampal neurogenesis. Line differences in HPA axis reactivity were maintained under fluoxetine treatment. However, we observed fluoxetine effects on glucocorticoid-induced negative feedback, stress-coping behaviours, cognitive functions and neurogenesis. Specifically, our results revealed line-dependent consequences of fluoxetine treatment: (1) an amelioration of the ‘melancholic-like’ features of HR mice (reversing the negative feedback resistance, the hyperactive coping style and the memory deficits; increasing hippocampal neurogenesis); (2) an exacerbation of the phenotypic deviations of LR mice (increasing their pronounced negative feedback and passive coping style). Thus, these findings support the predictive validity of antidepressant treatment in the HR mouse line and emphasize the translational value of the SR mouse model for the development of therapeutic strategies based on endophenotype-driven classifications

Corticosterone levels in high, intermediate and low stress reactive mice after exposure to a brief stressor.

<p><b><i>A & B</i></b><b>,</b> averaged values of plasma corticosterone concentration measured immediately before (pre stress-test: HR: 5±1.7, IR: 4±1.4, LR: 2.4±0.8) after the SRT (post stress-test: HR: 358±15, IR: 246±5, LR: 100±6) in mice genetically selected for differences in stress reactivity (N, HR: 8, IR: 8, LR: 8). ***<i>p</i><0.001 Bonferroni adj. <i>post-hoc</i> test. Values in ng/ml (mean±sem).</p

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

Hippocampal CA3 pyramidal neurons from high, low and intermediate reactive mice exhibit similar dendritic morphology.

<p><b><i>A</i></b><b>, </b><b><i>top</i></b>, coronal photomicrograph of the CA3 region from a Golgi-stained brain section. The white arrow indicates the position of the representative neuron shown at higher magnification below. <b><i>A, bottom</i></b>, dendritic trace of a typical CA3 pyramidal neuron is superimposed on its image. <b><i>B & E</i></b>, Sholl plots indicate the distribution of apical and basal dendritic length at increasing distance from the center of the cell body. <b><i>C, D, F, & G</i></b>, average values of total dendritic bifurcations (mean±sem, n, <i>apical</i>, HR: 11±1, 71; IR: 10±1, 57; LR: 10±1, 60; <i>basal</i>: HR: 9±1; IR: 8±1; LR: 9±1) and complexity (mean±sem, <i>apical</i>, HR: 68495±6972; IR: 68515±9960; LR: 58710±7856; <i>basal</i>, HR: 14360±1677; IR: 10365±1401; LR: 13387±2333) are similar in neurons from HR, IR, and LR mice.</p

Dendritic morphology of amygdala neurons is not different in high, intermediate and low stress reactivity mice.

<p><b><i>A</i></b><b>, </b><b><i>top</i></b>, representative photomicrograph of a Golgi-stained section containing the basolateral amygdala (<b><i>inset</i></b>: BLA is indicated by the white square on a hemisected coronal brain section). <b><i>A, bottom</i></b>, dendritic tracks of a sample BLA principal neuron (<i>white arrow</i>) is superimposed on its image. <b><i>B</i></b>, Sholl plots of dendritic length at increasing distance from the centre of the cell body is similar across groups. <b><i>C & D</i></b>, values of total basal dendritic bifurcations (mean±sem, n, HR:15±1, 35; IR:15±1, 32; LR:16±1, 19) and complexity (mean±sem, HR:21507±1988; IR:21521±1927; LR:20768±2965), averaged across cells, did not differ between groups.</p