Recovery of forearm and fine digit function after chronic spinal cord injury by simultaneous blockade of inhibitory matrix CSPG production and the receptor PTPσ

Spinal cord injuries (SCI), for which there are limited effective treatments, result in enduring paralysis and hypoesthesia, in part because of the inhibitory microenvironment that develops and limits regeneration/sprouting, especially during chronic stages. Recently, we discovered that targeted enzymatic removal of the inhibitory chondroitin sulfate proteoglycan (CSPG) component of the extracellular and perineuronal net (PNN) matrix via Chondroitinase ABC (ChABC) rapidly restored robust respiratory function to the previously paralyzed hemi-diaphragm after remarkably long times post-injury (up to 1.5 years) following a cervical level 2 lateral hemi-transection. Importantly, ChABC treatment at cervical level 4 in this chronic model also elicited improvements in gross upper arm function. In the present study, we focused on arm and hand function, seeking to highlight and optimize crude as well as fine motor control of the forearm and digits at lengthy chronic stages post-injury. However, instead of using ChABC, we utilized a novel and more clinically relevant systemic combinatorial treatment strategy designed to simultaneously reduce and overcome inhibitory CSPGs. Following a 3-month upper cervical spinal hemi-lesion using adult female Sprague Dawley rats, we show that the combined treatment had a profound effect on functional recovery of the chronically paralyzed forelimb and paw, as well as on precision movements of the digits. The regenerative and immune system related events that we describe deepen our basic understanding of the crucial role of CSPG-mediated inhibition via the PTPσ receptor in constraining functional synaptic plasticity at lengthy time points following SCI, hopefully leading to clinically relevant translational benefits

Age, worksite location, neuromodulators, and task performance in the ant Pheidole dentata

Social insect workers modify task performance according to age-related schedules of behavioral development, and/or changing colony labor requirements based on flexible responses that may be independent of age. Using known-age minor workers of the ant Pheidole dentata throughout 68 % of their 140-day laboratory lifespan, we asked whether workers found inside or outside the nest differed in task performance and if behaviors were correlated with and/or causally linked to changes in brain serotonin (5HT) and dopamine (DA). Our results suggest that task performance patterns of individually assayed minors collected at these two spatially different worksites were independent of age. Outside-nest minors displayed significantly higher levels of predatory behavior and greater activity than inside-nest minors, but these groups did not differ in brood care or phototaxis. We examined the relationship of 5HT and DA to these behaviors in known-age minors by quantifying individual brain titers. Both monoamines did not increase significantly from 20 to 95 days of age. DA did not appear to directly regulate worksite location, although titers were significantly higher in outside-nest than inside-nest workers. Pharmacological depletion of 5HT did not affect nursing, predation, phototaxis, or activity. Our results suggest that worker task capabilities are independent of age beyond 20 days, and only predatory behavior can be consistently predicted by spatial location. This could reflect worker flexibility or variability in the behavior of individuals collected at each location, which could be influenced by complex interactions between age, worksite location, social interactions, neuromodulators, and other environmental and internal regulators of behavior

Age, worksite location, neuromodulators, and task performance in the ant Pheidole dentata

Social insect workers modify task performance according to age-related schedules of behavioral development, and/or changing colony labor requirements based on flexible responses that may be independent of age. Using known-age minor workers of the ant Pheidole dentata throughout 68 % of their 140-day laboratory lifespan, we asked whether workers found inside or outside the nest differed in task performance and if behaviors were correlated with and/or causally linked to changes in brain serotonin (5HT) and dopamine (DA). Our results suggest that task performance patterns of individually assayed minors collected at these two spatially different worksites were independent of age. Outside-nest minors displayed significantly higher levels of predatory behavior and greater activity than inside-nest minors, but these groups did not differ in brood care or phototaxis. We examined the relationship of 5HT and DA to these behaviors in known-age minors by quantifying individual brain titers. Both monoamines did not increase significantly from 20 to 95 days of age. DA did not appear to directly regulate worksite location, although titers were significantly higher in outside-nest than inside-nest workers. Pharmacological depletion of 5HT did not affect nursing, predation, phototaxis, or activity. Our results suggest that worker task capabilities are independent of age beyond 20 days, and only predatory behavior can be consistently predicted by spatial location. This could reflect worker flexibility or variability in the behavior of individuals collected at each location, which could be influenced by complex interactions between age, worksite location, social interactions, neuromodulators, and other environmental and internal regulators of behavior

Inter-and intra-mouse variability in odor preferences revealed in an olfactory multiple choice test HHS Public Access

International audienceAnimals choose between sensory stimuli, a highly complex behavior which includes detection, discrimination, preference, and memory processes. Rodents are reported to display robust preferences for some odors, for instance in the context of choosing among possible mates or food items. In contrast to the apparent robustness of responses towards these and other 'ethologically relevant' odors, little is known about the robustness of behaviors towards odors which have no overt role in the rodent ecological niche, so-called 'non-ethologically relevant' odors. We developed an apparatus for monitoring the nose-poking behavior of mice and used this apparatus to explore the prevalence and stability of choices among different odors both across mice, and within mice over successive days. Mice were tested to either a panel of ethologically relevant or non-ethologically relevant odors in an olfactory multiple choice test. Significant preferences to non-ethologically relevant odors were observed across the population of mice, with longer investigation durations to some odors more than to others. However, we found substantial inter-mouse variability in these responses, and that responses to these odors even varied within mice across days of testing. Tests with ethologically-relevant odors revealed that responses towards these odors were also variable across mice, but within individual mice responses were somewhat stable. This work establishes an olfactory multiple choice test for monitoring odor investigation, choice, and preference behaviors and the application of this apparatus to assess across and within-mouse odor preference choice stability. These results highlight that odor preferences, as assayed by measuring choice behaviors, are variable

Lifespan behavioural and neural resilience in a social insect

International audienceAnalyses of senescence in social species are important to understanding how group living influences the evolution of ageing in society members. Social insects exhibit remarkable lifespan polyphenisms and division of labour, presenting excellent opportunities to test hypotheses concerning ageing and behaviour. Senescence patterns in other taxa suggest that behavioural performance in ageing workers would decrease in association with declining brain functions. Using the ant Pheidole dentata as a model, we found that 120-day-old minor workers, having completed 86% of their laboratory lifespan, showed no decrease in sensorimotor functions underscoring complex tasks such as alloparenting and foraging. Collaterally, we found no age-associated increases in apoptosis in functionally specialized brain compartments or decreases in synaptic densities in the mushroom bodies, regions associated with integrative processing. Furthermore, brain titres of serotonin and dopamine-neuromodulators that could negatively impact behaviour through age-related declines-increased in old workers. Unimpaired task performance appears to be based on the maintenance of brain functions supporting olfaction and motor coordination independent of age. Our study is the first to comprehensively assess lifespan task performance and its neurobiological correlates and identify constancy in behavioural performance and the absence of significant age-related neural declines

Data from: Lifespan behavioral and neural resilience in a social insect

Analyses of senescence in social species are important to understanding how group living influences the evolution of ageing in society members. Social insects exhibit remarkable lifespan polyphenisms and division of labour, presenting excellent opportunities to test hypotheses concerning ageing and behaviour. Senescence patterns in other taxa suggest that behavioural performance in ageing workers would decrease in association with declining brain functions. Using the ant Pheidole dentata as a model, we found that 120-day-old minor workers, having completed 86% of their laboratory lifespan, showed no decrease in sensorimotor functions underscoring complex tasks such as alloparenting and foraging. Collaterally, we found no age-associated increases in apoptosis in functionally specialized brain compartments or decreases in synaptic densities in the mushroom bodies, regions associated with integrative processing. Furthermore, brain titres of serotonin and dopamine—neuromodulators that could negatively impact behaviour through age-related declines—increased in old workers. Unimpaired task performance appears to be based on the maintenance of brain functions supporting olfaction and motor coordination independent of age. Our study is the first to comprehensively assess lifespan task performance and its neurobiological correlates and identify constancy in behavioural performance and the absence of significant age-related neural declines

Neural processing of the reward value of pleasant odorants

International audiencePleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics, we here report that stimulating the representation of pleasant odorants in a sensory structure, the pOB, can be rewarding, selfmotivating and is accompanied by ventral tegmental area activation. To explore the underlying neural circuitry downstream of the OB, we use 3D high-resolution imaging and optogenetics and determine that the pOB preferentially projects to the olfactory tubercle, whose increased activity is related to odorant attraction. We further show that attractive odorants act as reinforcers in dopamine-dependent place preference learning. Finally, we extend those findings to human, which exhibit place preference learning and an increase BOLD signal in the olfactory tubercle in response to attractive odorants. Thus, strong and persistent attraction induced by some odorants is due to a direct gateway from the pOB to the reward system

Brood care acts

Brood care act

Brood care time

Brood care tim

Predation

Predation was classified into 4 categories: 1= no aggression, 2= mandible flaring, 3= latent attack (delayed or not sustained for the duration the assay), 4= attack