Somatosensory stimuli trigger coordinated oxytocin neurons activity during social interaction

The hypothalamic neuropeptide oxytocin (OT) promotes social communication via its central release in the mammalian brain. However, how social interaction affects electrical activity of OT neurons is still unclear. To address this question, I used cell-type specific viral vectors in combination with optoelectrode-based techniques. I performed the in vivo single-unit recording of optically identified OT neurons in the paraventricular nucleus (PVN) of hypothalamus in adult female rats during their social interactions with unfamiliar female conspecifics. Simultaneously, we monitored behavior and recorded ultrasonic vocalizations. The results showed that active social interactions events induce an increase of PVN OT neurons spiking activity as well as a re-organization of the firing pattern from regular to bursting. The action potentials of simultaneously recorded OT neurons were synchronized and phase-locked with the PVN theta oscillations precisely at the time of social interactions, but not during non-social exploratory behavior. To decipher which sensory stimuli trigger OT neuron activity, I performed experiments with partial deprivation of specific sensory modalities. Direct physical contact between rats, or even gentle skin stimulation, led to a profound increase in OT firing rates. In contrast, presentation of visual, auditory and olfactory social-relevant stimuli alone did not significantly alter OT neuron activity. This led to the conclusion somatosensory component of social interaction drives OT neurons synchronous activity. To further explore the effects of tactile stimuli on the OT system, I examined the expression of the marker of neuronal activity c-Fos after repetitive somatosensory stimulation; it appeared to be significantly increased in a particular subpopulation of OT neurons named parvocellular OT neurons. Employing in-vivo calcium recording via fiber photometry, I investigated the role of parvocellular OT neurons in regulating the activity of the general population of PVN OT neurons, finding that parvocellular OT neurons mediate the activation of the OT system in response to somatosensory stimuli. Next, I selectively modulated the activity of parvocellular OT neurons in awake freely moving rats via pharmacogenetics: activation of this population of neurons resulted in increased social interaction, while inhibition leaded to decrease of social interaction. Finally, I studied the effect of intracerebral infusion of an OT receptor antagonist which induced a substantial reduction of social interaction time, even when parvocellular OT neurons were activated. Altogether, these results indicate that somatosensory stimulation is essential to activate OT neuron ensembles and, hence, can induce central neuropeptide release in socially interacting female rats. This opens perspectives for studying functional and anatomical connectivity between the somatosensory and OT systems in normal and psychopathological conditions

The Scaling of Human Contacts in Reaction-Diffusion Processes on Heterogeneous Metapopulation Networks

We present new empirical evidence, based on millions of interactions on Twitter, confirming that human contacts scale with population sizes. We integrate such observations into a reaction-diffusion metapopulation framework providing an analytical expression for the global invasion threshold of a contagion process. Remarkably, the scaling of human contacts is found to facilitate the spreading dynamics. Our results show that the scaling properties of human interactions can significantly affect dynamical processes mediated by human contacts such as the spread of diseases, and ideas

The scaling of human contacts and epidemic processes in metapopulation networks

We study the dynamics of reaction-diffusion processes on heterogeneous metapopulation networks where interaction rates scale with subpopulation sizes. We first present new empirical evidence, based on the analysis of the interactions of 13 million users on Twitter, that supports the scaling of human interactions with population size with an exponent γ ranging between 1.11 and 1.21, as observed in recent studies based on mobile phone data. We then integrate such observations into a reaction- diffusion metapopulation framework. We provide an explicit analytical expression for the global invasion threshold which sets a critical value of the diffusion rate below which a contagion process is not able to spread to a macroscopic fraction of the system. In particular, we consider the Susceptible-Infectious-Recovered epidemic model. Interestingly, the scaling of human contacts is found to facilitate the spreading dynamics. This behavior is enhanced by increasing heterogeneities in the mobility flows coupling the subpopulations. Our results show that the scaling properties of human interactions can significantly affect dynamical processes mediated by human contacts such as the spread of diseases, ideas and behaviors

A cortical mechanism linking saliency detection and motor reactivity in rhesus monkeys

: Sudden and surprising sensory events trigger neural processes that swiftly adjust behavior. To study the phylogenesis and the mechanism of this phenomenon, we trained two male rhesus monkeys to keep a cursor inside a visual target by exerting force on an isometric joystick. We examined the effect of surprising auditory stimuli on exerted force, scalp electroencephalographic (EEG) activity, and local field potentials (LFP) recorded from the dorso-lateral prefrontal cortex. Auditory stimuli elicited (1) a biphasic modulation of isometric force: a transient decrease followed by a corrective tonic increase, and (2) EEG and LFP deflections dominated by two large negative-positive waves (N70 and P130). The EEG potential was maximal at the scalp vertex, highly reminiscent of the human 'vertex potential'. Electrocortical potentials and force were tightly coupled: the P130 amplitude predicted the magnitude of the corrective force increase, particularly in the LFPs recorded from deep rather than superficial cortical layers. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to salient sensory events.Significance Statement Survival in the natural world depends on an animal's capacity to adapt ongoing behavior to unexpected events. To study the neural mechanisms underlying this capacity, we trained monkeys to apply constant force on a joystick while we recorded their brain activity from the scalp and, invasively, from the prefrontal cortex contralateral to the hand holding the joystick. Unexpected auditory stimuli elicited a biphasic force modulation: a transient reduction followed by a corrective adjustment. The same stimuli also elicited EEG and LFP responses, dominated by a biphasic wave that predicted the magnitude of the behavioral adjustment. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to unexpected events

Chemogenetic activation of oxytocin neurons: Temporal dynamics, hormonal release, and behavioral consequences

Chemogenetics provides cell type-specific remote control of neuronal activity. Here, we describe the application of chemogenetics used to specifically activate oxytocin (OT) neurons as representatives of a unique class of neuroendocrine cells. We injected recombinant adeno-associated vectors, driving the stimulatory subunit hM3Dq of a modified human muscarinic receptor into the rat hypothalamus to achieve cell type-specific expression in OT neurons. As chemogenetic activation of OT neurons has not been reported, we provide systematic analysis of the temporal dynamics of OT neuronal responses in vivo by monitoring calcium fluctuations in OT neurons, and intracerebral as well as peripheral release of OT. We further provide evidence for the efficiency of chemogenetic manipulation at behavioral levels, demonstrating that evoked activation of OT neurons leads to social motivation and anxiolysis. Altogether, our results will be profitable for researchers working on the physiology of neuroendocrine systems, peptidergic modulation of behaviors and translational psychiatry

Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons

Oxytocin (OT) is a great facilitator of social life but, although its effects on socially relevant brain regions have been extensively studied, OT neuron activity during actual social interactions remains unexplored. Most OT neurons are magnocellular neurons, which simultaneously project to the pituitary and forebrain regions involved in social behaviors. In the present study, we show that a much smaller population of OT neurons, parvocellular neurons that do not project to the pituitary but synapse onto magnocellular neurons, is preferentially activated by somatosensory stimuli. This activation is transmitted to the larger population of magnocellular neurons, which consequently show coordinated increases in their activity during social interactions between virgin female rats. Selectively activating these parvocellular neurons promotes social motivation, whereas inhibiting them reduces social interactions. Thus, parvocellular OT neurons receive particular inputs to control social behavior by coordinating the responses of the much larger population of magnocellular OT neurons. Charlet, Grinevich et al. show that social touch between female rats activates parvocellular oxytocin neurons; these neurons control social behavior by coordinating the responses of the much larger population of magnocellular oxytocin neurons