The habenula is an evolutionarily conserved structure of the vertebrate brain that is essential for behavioral flexibility and mood control. It is spontaneously active and is able to access diverse states when the animal is exposed to sensory stimuli. Here we investigate the dynamics of habenula spontaneous activity, to gain insight into how sensitivity is optimized. Two-photon calcium imaging was performed in resting zebrafish larvae at single-cell resolution. An analysis of avalanches of inferred spikes suggests that the habenula is subcritical. Activity had low covariance and a small mean, arguing against dynamic criticality. A multiple regression estimator of autocorrelation time suggests that the habenula is neither fully asynchronous nor perfectly critical, but is reverberating. This pattern of dynamics may enable integration of information and high flexibility in the tuning of network properties, thus providing a potential mechanism for the optimal responses to a changing environment.

Psychology and neuroscience research have shown that fractioning operations among several individuals along a hierarchical chain allows diffusing responsibility between components of the chain, which has the potential to disinhibit antisocial actions. Here, we present two studies, one using fMRI (Study 1) and one using EEG (Study 2), designed to help understand how commanding or being in an intermediary position impacts the sense of agency and empathy for pain. In the age of military drones, we also explored whether commanding a human or robot agent influences these measures. This was done within a single behavioral paradigm in which participants could freely decide whether or not to send painful shocks to another participant in exchange for money. In Study 1, fMRI reveals that activation in social cognition-related and empathy-related brain regions was equally low when witnessing a victim receive a painful shock while participants were either commander or simple intermediary transmitting an order, compare...

The rostral nucleus of the solitary tract (rNST), the initial CNS site for processing gustatory information, is comprised of two major cell types, glutamatergic excitatory and GABAergic inhibitory neurons. Although many investigators have described taste responses of rNST neurons, the phenotypes of these cells were unknown. To directly compare the response characteristics of both inhibitory and noninhibitory neurons, we recorded from mice expressing Channelrhodopsin-2 (ChR2) under the control of GAD65, a synthetic enzyme for GABA. We observed that chemosensitive profiles of GABAergic taste neurons (G+TASTE) were similar to non-GABA taste neurons (G-TASTE) but had much lower response rates. We further observed a novel subpopulation of GABA cells located more ventrally in the nucleus that were unresponsive to taste stimulation (G+UNR), suggesting pathways for inhibition initiated by centrifugal sources. This preparation also allowed us to determine how optogenetic activation of the rNST GABA network impacted...

In vitro and in vivo experimentation in the central nervous system are effective approaches to study its functioning. Manipulations in vitro are characterized by easy experimental control and stable experimental conditions. However, transferring these advantages to in vivo research remains technically and ethically challenging, preventing many research teams from acquiring critical recordings in their animal models. In order to transfer the benefits of in vitro experimentation to in vivo experimentation, we developed a suite of 3D-printed tools (a superfusion chamber with an independent brain presser and animal stand). Using the immature rat barrel cortex as a model, we show that our set of tools (further “superfusion preparation”) provides stable conditions for electrophysiological and neuroimaging recordings in the neonatal rat neocortex in vivo . Highly correlated intracellular and extracellular activity was recorded during spontaneous and evoked cortical activity, supporting the possibility of simultan...

The Emx1-IRES-Cre transgenic mouse is commonly used to direct genetic recombination in forebrain excitatory neurons. However, the original study reported that Emx1-Cre is also expressed embryonically in peripheral autonomic ganglia, which could potentially affect the interpretation of targeted circuitry contributing to systemic phenotypes. Here, we report that Emx1-Cre is expressed in the afferent vagus nerve system involved in autonomic cardiorespiratory regulatory pathways. Our imaging studies revealed expression of Emx1-Cre driven tdtomato fluorescence in the afferent vagus nerve innervating the dorsal medulla of brainstem, cell bodies in the nodose ganglion, and their potential target structures at the carotid bifurcation such as the carotid sinus and the superior cervical ganglion (SCG). Photostimulation of the afferent terminals in the nucleus tractus solitarius (NTS) in vitro using Emx1-Cre driven ChR2 reliably evoked EPSCs in the postsynaptic neurons with electrophysiological characteristics consis...

Music induces people to coordinate with one another. Here, we conduct two experiments to examine the underlying mechanism of the interbrain synchronization (IBS) that is induced by interpersonal coordination when people are exposed to musical beat and meter. In experiment 1, brain signals at the frontal cortex were recorded simultaneously from two participants of a dyad by using functional near-infrared spectroscopy (fNIRS) hyperscanning, while each tapped their fingers to aural feedback from their partner (coordination task) or from themselves (independence task) with and without the musical meter. The results showed enhanced IBS at the left-middle frontal cortex in case of the coordination task with musical beat and meter. The IBS was significantly correlated with the participants performance in terms of coordination. In experiment 2, we further examined the IBS while the participants coordinated their behaviors in various metrical contexts, such as strong and weak meters (i.e., high/low loudness of acou...

Many psychiatric diseases stem from an inability to cope with stressful events, as chronic stressors can precipitate or exacerbate psychopathologies. The neurobiological mechanisms underlying the response to chronic stress and the resulting anxiety states remain poorly understood. Stress neuropeptides in the extended amygdala circuitry mediate the behavioral response to stress, and hyperactivity of these systems has been hypothesized to be responsible for the emergence of persistent negative outcomes and for the pathogenesis of anxiety-related and trauma-related disorders. Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1R are highly expressed within the central amygdala (CeA) and play a key role in stress regulation. Here, we used chronic social defeat stress (CSDS), a clinically relevant model of psychosocial stress that produces robust maladaptive behaviors in rodents. We found that 10 days of CSDS cause a significant increase in PACAP levels selectively in the CeA of rats...

Dendritic spines are submicron, subcellular compartments whose shape is defined by actin filaments and associated proteins. Accurately mapping the cytoskeleton is a challenge, given the small size of its components. It remains unclear whether the actin-associated structures analyzed in dendritic spines of neurons in vitro apply to dendritic spines of intact, mature neurons in situ. Here, we combined advanced preparative methods with multitilt serial section electron microscopy (EM) tomography and computational analysis to reveal the full three-dimensional (3D) internal architecture of spines in the intact brains of male mice at nanometer resolution. We compared hippocampal (CA1) pyramidal cells and cerebellar Purkinje cells in terms of the length distribution and connectivity of filaments, their branching-angles and absolute orientations, and the elementary loops formed by the network. Despite differences in shape and size across spines and between spine heads and necks, the internal organization was remar...

The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity (NACA) in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that NACA influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathol...

Oral sensory neurons of the geniculate ganglion (GG) innervate taste papillae and buds on the tongue and soft palate. Electrophysiological recordings of these neurons and fibers revealed complexity in the number of unique response profiles observed, suggesting there are several distinct neuronal subtypes. Molecular descriptions of these subpopulations are incomplete. We report here the identification of a subpopulation of GG oral sensory neurons in mice by expression of tyrosine hydroxylase (TH). TH-expressing geniculate neurons represent 10–20% of oral sensory neurons and these neurons innervate taste buds in fungiform and anterior foliate taste papillae on the surface of the tongue, as well as taste buds in the soft palate. While 35–50% of taste buds on the tongue are innervated by these TH+ neurons, 100% of soft palate taste buds are innervated. These neurons did not have extragemmal processes outside of taste buds and did not express the mechanosensory neuron-associated gene Ret , suggesting they are c...