Predator Cat Odors Activate Sexual Arousal Pathways in Brains of Toxoplasma gondii Infected Rats

Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at first exposure, a presumed response to the evolutionary pressures of predation. Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat to sexually reproduce, this change in host behavior is thought to be a remarkable example of a parasite manipulating a mammalian host for its own benefit. Toxoplasma does not influence host response to non-feline predator odor nor does it alter behavior on olfactory, social, fear or anxiety tests, arguing for specific manipulation in the processing of cat odor. We report that Toxoplasma infection alters neural activity in limbic brain areas necessary for innate defensive behavior in response to cat odor. Moreover, Toxoplasma increases activity in nearby limbic regions of sexual attraction when the rat is exposed to cat urine, compelling evidence that Toxoplasma overwhelms the innate fear response by causing, in its stead, a type of sexual attraction to the normally aversive cat odor

Dynamic Expression of Cadherins Regulates Vocal Development in a Songbird

BACKGROUND: Since, similarly to humans, songbirds learn their vocalization through imitation during their juvenile stage, they have often been used as model animals to study the mechanisms of human verbal learning. Numerous anatomical and physiological studies have suggested that songbirds have a neural network called 'song system' specialized for vocal learning and production in their brain. However, it still remains unknown what molecular mechanisms regulate their vocal development. It has been suggested that type-II cadherins are involved in synapse formation and function. Previously, we found that type-II cadherin expressions are switched in the robust nucleus of arcopallium from cadherin-7-positive to cadherin-6B-positive during the phase from sensory to sensorimotor learning stage in a songbird, the Bengalese finch. Furthermore, in vitro analysis using cultured rat hippocampal neurons revealed that cadherin-6B enhanced and cadherin-7 suppressed the frequency of miniature excitatory postsynaptic currents via regulating dendritic spine morphology. METHODOLOGY/PRINCIPAL FINDINGS: To explore the role of cadherins in vocal development, we performed an in vivo behavioral analysis of cadherin function with lentiviral vectors. Overexpression of cadherin-7 in the juvenile and the adult stages resulted in severe defects in vocal production. In both cases, harmonic sounds typically seen in the adult Bengalese finch songs were particularly affected. CONCLUSIONS/SIGNIFICANCE: Our results suggest that cadherins control vocal production, particularly harmonic sounds, probably by modulating neuronal morphology of the RA nucleus. It appears that the switching of cadherin expressions from sensory to sensorimotor learning stage enhances vocal production ability to make various types of vocalization that is essential for sensorimotor learning in a trial and error manner

Expressions of Multiple Neuronal Dynamics during Sensorimotor Learning in the Motor Cortex of Behaving Monkeys

Previous studies support the notion that sensorimotor learning involves multiple processes. We investigated the neuronal basis of these processes by recording single-unit activity in motor cortex of non-human primates (Macaca fascicularis), during adaptation to force-field perturbations. Perturbed trials (reaching to one direction) were practiced along with unperturbed trials (to other directions). The number of perturbed trials relative to the unperturbed ones was either low or high, in two separate practice schedules. Unsurprisingly, practice under high-rate resulted in faster learning with more pronounced generalization, as compared to the low-rate practice. However, generalization and retention of behavioral and neuronal effects following practice in high-rate were less stable; namely, the faster learning was forgotten faster. We examined two subgroups of cells and showed that, during learning, the changes in firing-rate in one subgroup depended on the number of practiced trials, but not on time. In contrast, changes in the second subgroup depended on time and practice; the changes in firing-rate, following the same number of perturbed trials, were larger under high-rate than low-rate learning. After learning, the neuronal changes gradually decayed. In the first subgroup, the decay pace did not depend on the practice rate, whereas in the second subgroup, the decay pace was greater following high-rate practice. This group shows neuronal representation that mirrors the behavioral performance, evolving faster but also decaying faster at learning under high-rate, as compared to low-rate. The results suggest that the stability of a new learned skill and its neuronal representation are affected by the acquisition schedule.United States-Israel Binational Science FoundationIsrael Science FoundationIda Baruch FundRosetrees Trus

A Comparative Analysis Shows Morphofunctional Differences between the Rat and Mouse Melanin-Concentrating Hormone Systems

Sub-populations of neurons producing melanin-concentrating hormone (MCH) are characterized by distinct projection patterns, birthdates and CART/NK3 expression in rat. Evidence for such sub-populations has not been reported in other species. However, given that genetically engineered mouse lines are now commonly used as experimental models, a better characterization of the anatomy and morphofunctionnal organization of MCH system in this species is then necessary. Combining multiple immunohistochemistry experiments with in situ hybridization, tract tracing or BrdU injections, evidence supporting the hypothesis that rat and mouse MCH systems are not identical was obtained: sub-populations of MCH neurons also exist in mouse, but their relative abundance is different. Furthermore, divergences in the distribution of MCH axons were observed, in particular in the ventromedial hypothalamus. These differences suggest that rat and mouse MCH neurons are differentially involved in anatomical networks that control feeding and the sleep/wake cycle

Corticosterone Alters AMPAR Mobility and Facilitates Bidirectional Synaptic Plasticity

Background: The stress hormone corticosterone has the ability both to enhance and suppress synaptic plasticity and learning and memory processes. However, until today there is very little known about the molecular mechanism that underlies the bidirectional effects of stress and corticosteroid hormones on synaptic efficacy and learning and memory processes. In this study we investigate the relationship between corticosterone and AMPA receptors which play a critical role in activity-dependent plasticity and hippocampal-dependent learning. Methodology/Principal Findings: Using immunocytochemistry and live cell imaging techniques we show that corticosterone selectively increases surface expression of the AMPAR subunit GluR2 in primary hippocampal cultures via a glucocorticoid receptor and protein synthesis dependent mechanism. In agreement, we report that corticosterone also dramatically increases the fraction of surface expressed GluR2 that undergo lateral diffusion. Furthermore, our data indicate that corticosterone facilitates NMDAR-invoked endocytosis of both synaptic and extra-synaptic GluR2 under conditions that weaken synaptic transmission. Conclusion/Significance: Our results reveal that corticosterone increases mobile GluR2 containing AMPARs. The enhanced lateral diffusion properties can both facilitate the recruitment of AMPARs but under appropriate conditions facilitate the loss of synaptic AMPARs (LTD). These actions may underlie both the facilitating and suppressive effects of corticosteroid hormones on synaptic plasticity and learning and memory and suggest that these hormones accentuate synaptic efficacy

Cognitive Performances Are Selectively Enhanced during Chronic Caloric Restriction or Resveratrol Supplementation in a Primate

Effects of an 18-month treatment with a moderate, chronic caloric restriction (CR) or an oral supplementation with resveratrol (RSV), a potential CR mimetic, on cognitive and motor performances were studied in non-human primates, grey mouse lemurs (Microcebus murinus)

Age Affects the Expression of Maternal Care and Subsequent Behavioural Development of Offspring in a Precocial Bird

Variations of breeding success with age have been studied largely in iteroparous species and particularly in birds: survival of offspring increases with parental age until senescence. Nevertheless, these results are from observations of free-living individuals and therefore, it remains impossible to determine whether these variations result from parental investment or efficiency or both, and whether these variations occur during the prenatal or the postnatal stage or during both. Our study aimed first, to determine whether age had an impact on the expression of maternal breeding care by comparing inexperienced female birds of two different ages, and second, to define how these potential differences impact chicks’ growth and behavioural development. We made 22 2-month-old and 22 8-month-old female Japanese quail foster 1-day-old chicks. We observed their maternal behaviour until the chicks were 11 days old and then tested these chicks after separation from their mothers. Several behavioural tests estimated their fearfulness and their sociality. We observed first that a longer induction was required for young females to express maternal behaviour. Subsequently as many young females as elder females expressed maternal behaviour, but young females warmed chicks less, expressed less covering postures and rejected their chicks more. Chicks brooded by elder females presented higher growth rates and more fearfulness and sociality. Our results reveal that maternal investment increased with age independently of maternal experience, suggesting modification of hormone levels implied in maternal behaviour. Isolated effects of maternal experience should now be assessed in females of the same age. In addition, our results show, for first time in birds, that variations in maternal care directly induce important differences in the behavioural development of chicks. Finally, our results confirm that Japanese quail remains a great laboratory model of avian maternal behaviour and that the way we sample maternal behaviour is highly productive

Chimpanzees (Pan troglodytes) Fail a What-Where-When Task but Find Rewards by Using a Location-Based Association Strategy

Recollecting the what-where-when of an episode, or episodic-like memory, has been established in corvids and rodents. In humans, a linkage between remembering the past and imagining the future has been recognised. While chimpanzees can plan for the future, their episodic-like memory has hardly been investigated. We tested chimpanzees (Pan troglodytes) with an adapted food-caching paradigm. They observed the baiting of two locations amongst four and chose one after a given delay (15 min, 1 h or 5 h). We used two combinations of food types, a preferred and a less preferred food that disappeared at different rates. The subjects had to base their choices on the time elapsed since baiting, and on their memory of which food was where. They could recover either their preferred food or the one that remained present. All animals failed to obtain the preferred or present foods above chance levels. They were like-wise unsuccessful at choosing baited cups above chance levels. The subjects, thus, failed to use any feature of the baiting events to guide their choices. Nonetheless, their choices were not random, but the result of a developed location-based association strategy. Choices in the second half of the study correlated with the rewards obtained at each location in the first half of the study, independent from the choices made for each location in the first half of the study. This simple location-based strategy yielded a fair amount of food. The animals' failure to remember the what-where-when in the presented set-up may be due to the complexity of the task, rather than an inability to form episodic-like memories, as they even failed to remember what was where after 15 minutes

GABAA Receptor-Mediated Acceleration of Aging-Associated Memory Decline in APP/PS1 Mice and Its Pharmacological Treatment by Picrotoxin

Advanced age and mutations in the genes encoding amyloid precursor protein (APP) and presenilin (PS1) are two serious risk factors for Alzheimer's disease (AD). Finding common pathogenic changes originating from these risks may lead to a new therapeutic strategy. We observed a decline in memory performance and reduction in hippocampal long-term potentiation (LTP) in both mature adult (9–15 months) transgenic APP/PS1 mice and old (19–25 months) non-transgenic (nonTg) mice. By contrast, in the presence of bicuculline, a GABAA receptor antagonist, LTP in adult APP/PS1 mice and old nonTg mice was larger than that in adult nonTg mice. The increased LTP levels in bicuculline-treated slices suggested that GABAA receptor-mediated inhibition in adult APP/PS1 and old nonTg mice was upregulated. Assuming that enhanced inhibition of LTP mediates memory decline in APP/PS1 mice, we rescued memory deficits in adult APP/PS1 mice by treating them with another GABAA receptor antagonist, picrotoxin (PTX), at a non-epileptic dose for 10 days. Among the saline vehicle-treated groups, substantially higher levels of synaptic proteins such as GABAA receptor α1 subunit, PSD95, and NR2B were observed in APP/PS1 mice than in nonTg control mice. This difference was insignificant among PTX-treated groups, suggesting that memory decline in APP/PS1 mice may result from changes in synaptic protein levels through homeostatic mechanisms. Several independent studies reported previously in aged rodents both an increased level of GABAA receptor α1 subunit and improvement of cognitive functions by long term GABAA receptor antagonist treatment. Therefore, reduced LTP linked to enhanced GABAA receptor-mediated inhibition may be triggered by aging and may be accelerated by familial AD-linked gene products like Aβ and mutant PS1, leading to cognitive decline that is pharmacologically treatable at least at this stage of disease progression in mice

Antidepressants of the Serotonin-Antagonist Type Increase Body Fat and Decrease Lifespan of Adult Caenorhabditis elegans

It was recently suggested that specific antidepressants of the serotonin-antagonist type, namely mianserin and methiothepin, may exert anti-aging properties and specifically extend lifespan of the nematode C.elegans by causing a state of perceived calorie restriction (Petrascheck M, Ye X, Buck LB: An antidepressant that extends lifespan in adult Caenorhabditis elegans; Nature, Nov 22, 2007;450(7169):553–6, PMID 18033297). Using the same model organism, we instead observe a reduction of life expectancy when employing the commonly used, standardized agar-based solid-phase assay while applying the same or lower concentrations of the same antidepressants. Consistent with a well-known side-effect of these compounds in humans, antidepressants not only reduced lifespan but also increased body fat accumulation in C. elegans reflecting the mammalian phenotype. Taken together and in conflict with previously published findings, we find that antidepressants of the serotonin-antagonist type not only promote obesity, but also decrease nematode lifespan