The oxytocinergic and vasopressinergic systems regulate vital homeostatic functions as well as complex behaviors like social interaction. Despite their central neuromodulatory action, many details regarding the specification of the oxytocinergic and vasopressinergic circuits as well as the regulation of oxytocin (OXT) and vasopressin (AVP) release in the Central Nervous System remain unknown. Our laboratory has implemented a multidisciplinary approach combining genetic tagging for assaying OXT-containing vesicle dynamics and exocytosis, together with light-sheet ultraresolution microscopy and iDISCO+ tissue clarification methods for 3D circuit reconstruction (Madrigal & Jurado, 2021), in order to advance our current understanding of oxytocinergic and vasopressin function in modulating neuronal networks. We currently focus on analyzing the neurodevelopment of these systems and the dynamic properties of OXT and AVP release in the hypothalamus.Our results indicate a profound remodeling of the oxytocinergic and vasopressinergic systems during early postnatal stages that involves a switch of neuropeptide expression, which is recapitulated during vital experiences like aging or motherhood. Furthermore, OXT dynamics and release properties suggest distinct OXT-vesicle pools in the somatodendritic compartment of hypothalamic neurons which could be recruited upon diverse patterns of neuronal activity to orchestrate different aspects of behavior.
Background: Normal aging and many age-related disorders such as Alzheimer´s disease cause deficits in olfaction, however it is currently unknown how natural and pathological aging impact the detection of social odors which might contribute to the impoverishment of social behavior at old age further worsening overall health. Here, we investigated the effect of aging in the recognition of social cues and the display of social behavior. Methods: Social and non-social scents were employed to discern the specific impact of aging and neurodegeneration in social odor perception. Odor-evoked sniffing tests were employed to estimate the exploration time in response to social and non-social odors in naturally aged animals (up to 2-year-old senescent mice) and an animal model of Alzheimer´s disease (APP/PS1). Social habituation-dishabituation tests were adapted to determine short- and long-term social discrimination, the effect of previous experience in social recognition and potential disruptions of self-awareness. Sociability and social novelty were analyzed by a three chamber test. Mature (OMP) and proliferating (Sox2, PCNA) neurons in the vomeronasal organ were analyzed by immunostaining and stereology during healthy and pathological aging. Results: Our findings indicate that aging distinctively disrupts the processing of social olfactory cues decreasing social odor exploration, discrimination and habituation in both wild type senescent (2-year-old) mice and in 1-year-old double mutant model of Alzheimer´s disease (APP/PS1). Furthermore, social novelty was diminished in 1-year-old APP/PS1 mice, indicating that alterations in the processing of social cues are accelerated during pathological aging. Analysis of the vomeronasal organ, the main gateway to pheromone-encoded information, indicated that natural and pathological aging distinctively affect the neurogenic ability of the vomeronasal sensory epithelium. Whereas cell proliferation remained majorly preserved in 1-year-old APP/PS1 mice, naturally aged animals exhibited significant deficiencies in the number of mature, proliferative and progenitor cells. Conclusions: This study reveals fundamental differences in the cellular processes by which natural and pathological aging disrupt the exploration of social information and social behavior.
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