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...

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...

Oscillatory activity in the human brain is dominated by posterior alpha oscillations (8–14 Hz), which have been shown to be functionally relevant in a wide variety of cognitive tasks. Although posterior alpha oscillations are commonly considered a single oscillator anchored at an individual alpha frequency (∼10 Hz), previous work suggests that individual alpha frequency reflects a spatial mixture of different brain rhythms. In this study, we assess whether independent component analysis (ICA) can disentangle functionally distinct posterior alpha rhythms in the context of visual short-term memory retention. Magnetoencephalography (MEG) was recorded in 33 subjects while performing a visual working memory task. Group analysis at sensor level suggested the existence of a single posterior alpha oscillator that increases in power and decreases in frequency during memory retention. Conversely, single-subject analysis of independent components revealed the existence of two dissociable alpha rhythms: one that incre...

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...

Birds are exceptionally adept at controlling their body position. For example, they can coordinate rapid movements of their body while stabilizing their head. Intriguingly, this ability may rely in part on a mechanosensory organ in the avian lower spinal cord called the lumbosacral organ (LSO). However, molecular mechanotransduction mechanisms have not been identified in the avian spinal cord. Here, we report the presence of glycinergic neurons in the LSO that exhibit immunoreactivity for myosin7a and espin, molecules essential for function and maintenance of hair cells in the inner ear. Specifically, we find glycinergic cell bodies near the central canal and processes that extend laterally to the accessory lobes and spinal ligaments. These LSO neurons are reminiscent of glycinergic neurons in a recently-described lateral spinal proprioceptive organ in zebrafish that detects spinal bending. The avian LSO, however, is located inside a series of fused vertebrae called the synsacrum, which constrains spinal b...

Learning and memory requires coordinated activity between different regions of the brain. Here, we studied the interaction between infralimbic medial prefrontal cortex (mPFC) and hippocampal dorsal CA1 during associative odorant discrimination learning in the mouse. We found that as the animal learns to discriminate odorants in a go-no go task, the coupling of high-frequency neural oscillations to the phase of θ oscillations (θ-referenced phase-amplitude coupling or tPAC) changes in a manner that results in divergence between rewarded and unrewarded odorant-elicited changes in the θ phase-referenced power (tPRP) for β and γ oscillations. In addition, in the proficient animal there was a decrease in the coordinated oscillatory activity between CA1 and mPFC in the presence of the unrewarded odorant. Furthermore, the changes in tPAC resulted in a marked increase in the accuracy for decoding contextual odorant identity from tPRP when the animal became proficient. Finally, we studied the role of Ca2+/calmodulin...

Severe brain metabolic dysfunction and amyloid-β accumulation are key hallmarks of Alzheimer’s disease (AD). While astrocytes contribute to both pathologic mechanisms, the role of their mitochondria, which is essential for signaling and maintenance of these processes, has been largely understudied. The current work provides the first direct evidence that the mitochondrial metabolic switch 17β-hydroxysteroid dehydrogenase type 10 (17βHSD10) is expressed and active in murine astrocytes from different brain regions. While it is known that this protein is overexpressed in the brains of AD patients, we found that 17βHSD10 is also upregulated in astrocytes exposed to amyloidogenic and ischemic stress. Importantly, such catalytic overexpression of 17βHSD10 inhibits mitochondrial respiration during increased energy demand. This observation contrasts with what has been found in neuronal and cancer model systems, which suggests astrocyte-specific mechanisms mediated by the protein. Furthermore, the catalytic upregul...