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 (LFPs) recorded from the dorsolateral 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 symmetrical and 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 corticomotor 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 abrupt 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 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 corticomotor mechanism supporting adaptive behavior in response to unexpected events.

Viral vectors for opto-electrode recording and photometry-based imaging of oxytocin neurons in anesthetized and socially interacting rats.

Here, we present a step-by-step protocol to target, record, and manipulate the activity of oxytocin neurons in awake rats. The protocol includes a procedure to record the activity of oxytocin neurons from awake and socially interacting rats using opto-electrodes for simultaneous electrophysiological recording and virally based cell-type-specific opto-tagging with Channelrhodopsin 2. Furthermore, we illustrate a procedure for optically guided implantation of optic fiber and imaging of oxytocin neuron population activity expressing calcium indicator GCaMP6s with the fiber photometry technique. For complete details on the use and execution of this protocol, please refer to Tang et al., 2020.

Oxytocinergic Feedback Circuitries: An Anatomical Basis for Neuromodulation of Social Behaviors.

Oxytocin (OT) is a neuropeptide produced by hypothalamic neurons and is known to modulate social behavior among other functions. Several experiments have shown that OT modulates neuronal activity in many brain areas, including sensory cortices. OT neurons thus project axons to various cortical and subcortical structures and activate neuronal subpopulations to increase the signal-to-noise ratio, and in turn, increases the saliency of social stimuli. Less is known about the origin of inputs to OT neurons, but recent studies show that cells projecting to OT neurons are often located in regions where the OT receptor (OTR) is expressed. Thus, we propose the existence of reciprocal connectivity between OT neurons and extrahypothalamic OTR neurons to tune OT neuron activity depending on the behavioral context. Furthermore, the latest studies have shown that OTR-expressing neurons located in social brain regions also project to other social brain regions containing OTR-expressing neurons. We hypothesize that OTR-expressing neurons across the brain constitute a common network coordinated by OT.

Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents.

Oxytocin (OT) orchestrates social and emotional behaviors through modulation of neural circuits. In the central amygdala, the release of OT modulates inhibitory circuits and, thereby, suppresses fear responses and decreases anxiety levels. Using astrocyte-specific gain and loss of function and pharmacological approaches, we demonstrate that a morphologically distinct subpopulation of astrocytes expresses OT receptors and mediates anxiolytic and positive reinforcement effects of OT in the central amygdala of mice and rats. The involvement of astrocytes in OT signaling challenges the long-held dogma that OT acts exclusively on neurons and highlights astrocytes as essential components for modulation of emotional states under normal and chronic pain conditions.

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.

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.

Distinct Types of Feeding Related Neurons in Mouse Hypothalamus.

The last two decades of research provided evidence for a substantial heterogeneity among feeding-related neurons (FRNs) in the hypothalamus. However, it remains unclear how FRNs differ in their firing patterns during food intake. Here, we investigated the relationship between the activity of neurons in mouse hypothalamus and their feeding behavior. Using tetrode-based in vivo recording technique, we identified various firing patterns of hypothalamic FRNs, which, after the initiation of food intake, can be sorted into four types: sharp increase (type I), slow increase (type II), sharp decrease (type III), and sustained decrease (type IV) of firing rates. The feeding-related firing response of FRNs was rigidly related to the duration of food intake and, to a less extent, associated with the type of food. The majority of these FRNs responded to glucose and leptin and exhibited electrophysiological characteristics of putative GABAergic neurons. In conclusion, our study demonstrated the diversity of neurons in the complex hypothalamic network coordinating food intake.

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.