Children exposed prenatally to opioids are at an increased risk for behavioral problems and executive function deficits. The prefrontal cortex (PFC) and amygdala (AMG) regulate executive function and social behavior and are sensitive to opioids prenatally. Opioids can bind to toll-like receptor 4 (TLR4) to activate microglia, which may be developmentally important for synaptic pruning. Therefore, we tested the effects of perinatal morphine exposure on executive function and social behavior in male and female mouse offspring, along with microglial-related and synaptic-related outcomes. Dams were injected once daily subcutaneously with saline ( n  = 8) or morphine (MO; 10 mg/kg; n  = 12) throughout pregestation, gestation, and lactation until offspring were weaned on postnatal day 21 (P21). Male MO offspring had impairments in attention and accuracy in the five-choice serial reaction time task, while female MO offspring were less affected. Targeted gene expression analysis at P21 in the PFC identified altera...

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...

The subthalamic nucleus (STN) is a small, excitatory nucleus that regulates the output of basal ganglia motor circuits. The functions of the STN and its role in the pathophysiology of Parkinson’s disease are now well established. However, some basic characteristics like the developmental origin and molecular phenotype of neuronal subpopulations are still being debated. The classical model of forebrain development attributed the origin of STN within the diencephalon. Recent studies of gene expression patterns exposed shortcomings of the classical model. To accommodate these findings, the prosomeric model was developed. In this concept, STN develops within the hypothalamic primordium, which is no longer a part of the diencephalic primordium. This concept is further supported by the expression patterns of many transcription factors. It is interesting to note that many transcription factors involved in the development of the STN are also involved in the pathogenesis of neurodevelopmental disorders. Thus, the s...

Compromised endocytosis in neurons leads to synapse overgrowth and altered organization of synaptic proteins. However, the molecular players and the signaling pathways which regulate the process remain poorly understood. Here, we show that σ2-adaptin, one of the subunits of the AP2-complex, genetically interacts with Mad, Medea and Dad (components of BMP signaling) to control neuromuscular junction (NMJ) growth in Drosophila . Ultrastructural analysis of σ2-adaptin mutants show an accumulation of large vesicles and membranous structures akin to endosomes at the synapse. We found that mutations in σ2-adaptin lead to an accumulation of Tkv receptors at the presynaptic membrane. Interestingly, the level of small GTPase Rab11 was significantly reduced in the σ2-adaptin mutant synapses. However, expression of Rab11 does not restore the synaptic defects of σ2-adaptin mutations. We propose a model in which AP2 regulates Tkv internalization and endosomal recycling to control synaptic growth.

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...

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 pathophysiological features of ischemia-related blood–brain barrier (BBB) disruption are widely studied using preclinical stroke models. However, in many of these models, craniectomy is required to confirm arterial occlusion via laser Doppler flowmetry or to enable direct ligation of the cerebral artery. In the present study, mice were used to construct a distal middle cerebral artery occlusion (dMCAO) model, a preclinical stroke model that requires craniectomy to enable direct ligation of the cerebral artery, or were subjected to craniectomy alone. dMCAO but not craniectomy caused neurodegeneration and cerebral infarction, but both procedures induced an appreciable increase in BBB permeability to Evans blue dye, fluorescein, and endogenous albumin but not to 10 kDa dextran-FITC, leading to cerebral edema. Using rats, we further showed that BBB disruption induced by craniectomy with no evidence of dural tearing was comparable to that induced by craniectomy involving tearing of the dura. In conclusion, ...

In real-world decision-making scenarios, negative consequences do not always occur immediately after a choice. This delay between action and outcome drives the underestimation, or “delay discounting,” of punishment. While the neural substrates underlying sensitivity to immediate punishment have been well-studied, there has been minimal investigation of delayed consequences. Here, we assessed the role of lateral orbitofrontal cortex (LOFC) and basolateral amygdala (BLA), two regions implicated in cost/benefit decision-making, in sensitivity to delayed versus immediate punishment. The delayed punishment decision-making task (DPDT) was used to measure delay discounting of punishment in rodents. During DPDT, rats choose between a small, single-pellet reward and a large, three-pellet reward accompanied by a mild foot shock. As the task progresses, the shock is preceded by a delay that systematically increases or decreases throughout the session. We observed that rats avoid choices associated with immediate puni...

The functional magnetic resonance imaging under naturalistic paradigm (NfMRI) showed great advantages in identifying complex and interactive functional brain networks (FBNs) because of its dynamics and multimodal information. In recent years, various deep learning models, such as deep convolutional autoencoder (DCAE), deep belief network (DBN), and volumetric sparse DBN (vsDBN), can obtain hierarchical FBNs and temporal features from fMRI data. Among them, the vsDBN model revealed a good capability in identifying hierarchical FBNs by modeling fMRI volume images. However, because of the high dimensionality of fMRI volumes and the diverse training parameters of deep learning methods, especially the network architecture that is the most critical parameter for uncovering the hierarchical organization of human brain function, researchers still face challenges in designing an appropriate deep learning framework with automatic network architecture optimization to model volumetric NfMRI. In addition, most of the e...

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.