Biology subjects

Carcea, I.

Publications and source records attributed to Carcea, I..

8 recordsLinked to original sources

bioRxiv2025

Susceptibility of Glucose Regulation to Social Isolation

Loneliness and social isolation strongly associate with increased incidence of diabetes in humans. However, it remains unclear if lack of meaningful social interactions represents a cause or a symptom of disease. In rodents, social isolation leads to metabolic dysregulation, however the dynamics and contributing factors remain poorly understood. Here we show that single-housing young adult male mice for at least three weeks led to fasting hyperglycemia, an effect that was maintained for the duration of single-housing, but was corrected within a week of reverting mice to co-housing conditions. Single-housing did not affect glucose regulation in females. Gonadectomy experiments revealed that testicular factors induced susceptibility to social isolation, as orchiectomy prevented isolation-induced fasting hyperglycemia in males. We did not find a protective role for ovarian hormones, as ovariectomized females were as resilient as intact females to isolation-induced fasting hyperglycemia. To understand the underlying mechanisms for susceptibility to isolation, we measured plasma levels of glucoregulatory hormones. Isolation did not affect the levels of insulin, epinephrine, and corticosterone. However, glucagon levels were distinctly modulated by social isolation in intact and orchiectomized mice. Social isolation induces increased immediate early gene expression in specific neurons of the ventromedial hypothalamus, a glucoregulatory brain structure that promotes glucagon release. Taken together, our findings show that testicular hormones make males susceptible to isolation-induced disruption of glucose regulation and suggest that brain glucoregulatory neurons play a role.

systems biology↗

bioRxiv2025

Hypothalamic Vasopressin Neurons Enable Maternal Thermoregulatory Behaviors

Newborns of many mammalian species are partial poikilotherms and require adult thermoregulatory care for survival. In mice, pup survival in cold and cool ambient temperature depends on the ability of adult caregivers to huddle pups and bring them into a high-quality nest. It is therefore essential that adult mice adjust parental care as a function of changes in ambient temperature. Here, we investigated how mouse maternal care adapts to a range of temperatures, from cold to warm. We show that changes in ambient temperature affect several individual and co-parenting maternal behaviors in both dams and virgin female mice, and modulate activity of vasopressin neurons. Furthermore, we establish that the effects of ambient temperature on both maternal care and the activity of vasopressin neurons depend in part on thermosensation, specifically on the TRPM8 sensor. Using trans-synaptic anterograde tracing and whole-brain activity mapping, we find that vasopressin neurons from the paraventricular hypothalamic nucleus connect synaptically with temperature-responsive brain structures implicated in maternal care. We then show that optogenetic activation of vasopressin projections to the central amygdala, a structure activated by cold ambient temperature, recapitulates the effects of cold on co-parenting behaviors. Our data provide a biological mechanism for maternal thermoregulatory behavior in mice with translational relevance to the reported association between ecosystem temperature fluctuations and variations in human child neglect cases.

neuroscience↗

bioRxiv2022

Evaluating sickness-induced anxiety versus lethargy at the behavioral and neuronal activity level

In mammals, inflammatory responses to infections trigger adaptive behavioral changes collectively known as sickness behavior. Among these, lethargy protects the sick individual by conserving energy, and increased anxiety is believed to prevent exposure to threats. However, the characterization of these conflicting behavioral states in sickness could be an artifact of behavioral assessment, particularly in rodents. We adjusted existing behavioral testing and designed a new paradigm to disambiguate between increased lethargy versus increased anxiety. Our data indicate that in mice sickness induces a significant increase in lethargy but not in anxiety. Further supporting our behavioral results, at the neuronal level we found evidence that sickness activates anxiolytic rather than anxiogenic regions of the amygdala, including oxytocin receptor expressing neurons. Putative mechanisms by which sickness could activate CeA-OTR+ neurons were investigated.

neuroscience↗

bioRxiv2021

Neural networks implicated in autobiographical memory training

Training of autobiographical memory has been proposed as intervention to improve cognitive functions. The neural substrates for such improvements are poorly understood. Several brain networks have been previously linked to autobiographical recollections, including the default mode network (DMN) and the sensorimotor network. Here we tested the hypothesis that different neural networks support distinct aspects of memory improvement in response to training on a group of 59 subjects. We found that memory training increases DMN connectivity, and this associates with improved recollection of cue-specific memories. On the contrary, training decreased connectivity in the sensorimotor network, a decrease that correlated with improved ability for voluntary recall. Moreover, only decreased sensorimotor connectivity associated with training-induced decrease in the TNF immunological factor, which has been previously linked to improved cognitive performance. We identified functional and biochemical factors that associate with distinct memory processes improved by autobiographical training. Pathways which connect autobiographical memory to both high level cognition and somatic physiology are discussed.

neuroscience↗

bioRxiv2021

Perinatal Inflammation Disturbs Secondary Germinal Zone Neurogenesis and Gliogenesis Producing Deficits in Sociability

Epidemiologic studies have demonstrated that infections during pregnancy increase the risk of offspring developing Schizophrenia, Autism, Depression and Bipolar Disorder and have implicated interleukin-6 (IL-6) as a causal agent. However, other cytokines have been associated with psychiatric disorders; therefore, it remains to be established whether elevating IL-6 is sufficient to alter the trajectory of neural development. Furthermore, most rodent studies have manipulated the maternal immune system at mid-gestation, which affects the stem cells and progenitors in both the primary and secondary germinal matrices. Therefore, a question that remains to be addressed is whether elevating IL-6 when the secondary germinal matrices are most active will affect brain development. Here, we have increased IL-6 from postnatal days 3-6, when the secondary germinal matrices are rapidly expanding. Using Nestin-CreERT2 fate mapping we show that this transient increase in IL-6 decreased neurogenesis in the dentate gyrus of the dorsal hippocampus, reduced astrogliogenesis in the prefrontal cortex and amygdala and decreased oligodendrogenesis in the body and splenium of the corpus callosum all by [~]50%. Moreover, the IL-6 treatment elicited behavioral changes classically associated with neurodevelopmental disorders. As adults, IL-6 injected male mice lost social preference in the social approach test, spent [~]30% less time socially engaging with sexually receptive females and produced [~]50% fewer ultrasonic vocalizations during mating. They also engaged [~]50% more time in self-grooming behavior and had an increase in inhibitory avoidance. Altogether, these data provide new insights into the biological mechanisms linking perinatal immune activation to complex neurodevelopmental brain disorders. Significance statementIn these studies, we doubled circulating IL-6 levels in mice from postnatal days 3-6 to test the hypothesis that this would be sufficient to disturb neural development. More specifically, we hypothesized that IL-6 would affect postnatal neural stem cell and progenitor expansion and specification. We show that this transient increase in IL-6 decreases the numbers of granule neurons in the dorsal hippocampus, astrocytes in the prefrontal cortex and amygdala and oligodendrocytes in the corpus callosum. Importantly, this transient increase in IL-6 changes the sociability, communication and repetitive behaviors of the treated mice as adults, which are core symptoms pertinent to several neurodevelopmental psychiatric disorders.

neuroscience↗

bioRxiv2021

Spontaneous thought and microstate activity modulation by social imitation

Social imitation increases well-being and closeness by mechanisms that remain poorly understood. We propose that imitation impacts behavioural states in part by modulating post-imitation mind-wandering. The human mind wanders spontaneously and frequently, revisiting the past and imagining the future of self and of others. External and internal factors can influence wandering spontaneous thoughts, whose content predicts subsequent emotional states. In 43 young subjects, we find that imitating the arm movements of an actor alters the dynamics and the content of subsequent resting-state spontaneous thoughts. Imitation-sensitive features of spontaneous thoughts correlate with both behavioural states and salivary oxytocin levels. EEG microstate analysis reveals that global patterns of correlated neuronal activity predict imitation-induced changes in spontaneous thoughts. Thus, imitation can modulate ongoing activity in specific neural networks to change spontaneous thought patterns as a function of oxytocin levels, and to ultimately orchestrate behavioural states.

neuroscience↗

bioRxiv2019

Oxytocin Neurons Enable Social Transmission of Maternal Behavior

Maternal care is profoundly important for mammalian survival, and non-biological parents can express it after experience with infants. One critical molecular signal for maternal behavior is oxytocin, a hormone centrally released by hypothalamic paraventricular nucleus (PVN). Oxytocin enables plasticity within the auditory cortex, a necessary step for responding to infant vocalizations. To determine how this change occurs during natural experience, we continuously monitored homecage behavior of female virgin mice co-housed for days with an experienced mother and litter, synchronized with recordings from virgin PVN cells, including from oxytocin neurons. Mothers engaged virgins in maternal care by ensuring their nest presence, and demonstrated maternal behavior in self-generated pup retrieval episodes. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup vocalizations. Thus rodents can acquire maternal behavior by social transmission, and our results describe a mechanism for adapting brains of adult caregivers to infant needs via endogenous oxytocin. One Sentence SummaryMother mice help co-housed virgins become maternal by enacting specific behaviors that activate virgin oxytocin neurons.

neuroscience↗

bioRxiv2018

Nominally non-responsive frontal and sensory cortical cells encode task-relevant variables via ensemble consensus-building

Neurons recorded in behaving animals often do not discernibly respond to sensory input and are not overtly task-modulated. These nominally non-responsive neurons are difficult to interpret and are typically neglected from analysis, confounding attempts to connect neural activity to perception and behavior. Here we describe a trial-by-trial, spike-timing-based algorithm to reveal the hidden coding capacities of these neurons in auditory and frontal cortex of behaving rats. Responsive and nominally non-responsive cells contained significant information about sensory stimuli and behavioral decisions, and network modeling indicated that nominally non-responsive cells are important for task performance. Sensory input was more accurately represented in frontal cortex than auditory cortex, via ensembles of nominally non-responsive cells coordinating the behavioral meaning of spike timings on correct but not error trials. This unbiased approach allows the contribution of all recorded neurons - particularly those without obvious task-modulation - to be assessed for behavioral relevance on single trials.

neuroscience↗