Recent connectome analyses of the entire synaptic circuit in the nervous system have provided tremendous insights into how neural processing occurs through the synaptic relay of neural information. Conversely, the extent to which ephaptic transmission which does not depend on the synapses contributes to the relay of neural information, especially beyond a distance between adjacent neurons and to neural processing remains unclear. We show that ephaptic transmission mediated by extracellular potential changes in female Drosophila melanogaster can reach more than 200 μm, equivalent to the depth of its brain. Furthermore, ephaptic transmission driven by retinal photoreceptor cells mediates light-evoked firing rate increases in olfactory sensory neurons. These results indicate that ephaptic transmission contributes to sensory responses that can change momentarily in a context-dependent manner. SIGNIFICANCE STATEMENT: Although extracellular field potential activities are commonly observed in many nervous syst...

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. SIGNIFICANCE STATEMEN...

Many controlled, in vitro studies have demonstrated how postsynaptic responses to presynaptic spikes are not constant but depend on short-term synaptic plasticity (STP) and the detailed timing of presynaptic spikes. However, the effects of short-term plasticity (depression and facilitation) are not limited to short, sub-second timescales. The effects of STP appear on long timescales as changes in presynaptic firing rates lead to changes in steady-state synaptic transmission. Here we examine the relationship between natural variations in the presynaptic firing rates and spike transmission in vivo . Using large-scale spike recordings in awake male and female mice from the Allen Institute Neuropixels dataset, we first detect putative excitatory synaptic connections based on cross-correlations between the spike trains of millions of pairs of neurons. For the subset of pairs where a transient, excitatory effect was detected, we use a model-based approach to track fluctuations in synaptic efficacy and find that ...

Electrical activity in neurons is highly energy demanding and accompanied by rises in cytosolic Ca2+. Cytosolic Ca2+, in turn, secures energy supply by pushing mitochondrial metabolism either through augmented NADH (nicotinamide adenine dinucleotide) transfer into mitochondria via the malate–aspartate shuttle (MAS) or via direct activation of dehydrogenases of the TCA cycle after passing into the matrix through the mitochondrial Ca2+ uniporter (MCU). Another Ca2+-sensitive booster of mitochondrial ATP synthesis is the glycerol-3-phosphate shuttle (G3PS), whose role in neuronal energy supply has remained elusive. Essential components of G3PS are expressed in hippocampal neurons. Single neuron metabolic measurements in primary hippocampal cultures derived from rat pups of either sex reveal only moderate, if any, constitutive activity of G3PS. However, during electrical activity neurons fully rely on G3PS when MAS and MCU are unavailable. Under these conditions, G3PS is required for appropriate action potenti...

Tactile sensations can bias visual perception in the awake state while visual sensitivity is known to be facilitated by sleep. It remains unknown, however, whether the tactile sensation during sleep can bias the visual improvement after sleep. Here, we performed nap experiments in human participants ( n = 56, 18 males, 38 females) to demonstrate that repetitive tactile motion stimulation on the fingertip during slow wave sleep selectively enhanced subsequent visual motion detection. The visual improvement was associated with slow wave activity. The high activation at the high beta frequency was found in the occipital electrodes after the tactile motion stimulation during sleep, indicating a visual-tactile cross-modal interaction during sleep. Furthermore, a second experiment ( n = 14, 14 females) to examine whether a hand- or head-centered coordination is dominant for the interpretation of tactile motion direction showed that the biasing effect on visual improvement occurs according to the hand-centered co...

Motor units convert the last neural code of movement into muscle forces. The classic view of motor unit control is that the CNS sends common synaptic inputs to motoneuron pools and that motoneurons respond in an orderly fashion dictated by the size principle. This view, however, is in contrast with the large number of dimensions observed in motor cortex, which may allow individual and flexible control of motor units. Evidence for flexible control of motor units may be obtained by tracking motor units longitudinally during tasks with some level of behavioral variability. Here we identified and tracked populations of motor units in the brachioradialis muscle of two macaque monkeys during 10 sessions spanning >1 month with a broad range of rate of force development (1.8–38.6 N · m · s−1). We found a very stable recruitment order and discharge characteristics of the motor units over sessions and contraction trials. The small deviations from orderly recruitment were fully predicted by the motor unit recruitment...

The intraparietal sulcus (IPS) has been implicated in numerous functions that range from representation of visual stimuli to action planning, but its role in abstract decision-making has been unclear, in part because low-level functions often act as confounds. Here, we address this problem using a task that dissociates abstract decision-making from sensory salience, attentional control, motor planning, and motor output. Functional MRI data were collected from healthy female and male human subjects while they performed a policy abstraction task requiring use of a more abstract (second-order) rule to select between two less abstract (first-order) rules that informed the motor response. By identifying IPS subdivisions with preferential connectivity to prefrontal regions that are differentially responsive to task abstraction, we found that a caudal IPS (cIPS) subregion with strongest connectivity to the pre-premotor cortex was preferentially active for second-order cues, whereas a rostral IPS subregion (rIPS) ...

A particularly elusive puzzle concerning the hippocampus is how the structural differences along its long anteroposterior axis might beget meaningful functional differences, particularly in terms of the granularity of information processing. One measure posits to quantify this granularity by calculating the average statistical independence of the BOLD signal across neighboring voxels, or intervoxel similarity (IVS), and has shown the anterior hippocampus to process coarser-grained information than the posterior hippocampus. This measure, however, has yielded opposing results in studies of developmental and healthy aging samples, which also varied in fMRI acquisition parameters and hippocampal parcellation methods. To reconcile these findings, we measured IVS across two separate resting-state fMRI acquisitions and compared the results across many of the most widely used parcellation methods in a large young-adult sample of male and female humans (Acquisition 1, N = 233; Acquisition 2, N = 176). Finding conf...

To understand language, we must infer structured meanings from real-time auditory or visual signals. Researchers have long focused on word-by-word structure building in working memory as a mechanism that might enable this feat. However, some have argued that language processing does not typically involve rich word-by-word structure building, and/or that apparent working memory effects are underlyingly driven by surprisal (how predictable a word is in context). Consistent with this alternative, some recent behavioral studies of naturalistic language processing that control for surprisal have not shown clear working memory effects. In this fMRI study, we investigate a range of theory-driven predictors of word-by-word working memory demand during naturalistic language comprehension in humans of both sexes under rigorous surprisal controls. In addition, we address a related debate about whether the working memory mechanisms involved in language comprehension are language specialized or domain general. To do so...

Sensory responses typically vary depending on the recent history of sensory experience. This is essential for processes, including adaptation, efficient coding, and change detection. In the auditory cortex (AC), the short-term history dependence of sound-evoked (onset) responses has been well characterized. Yet many AC neurons also respond to sound terminations, and little is known about the history dependence of these “offset” responses, whether the short-term dynamics of onset and offset responses are correlated, or how these properties are distributed among cell types. Here we presented awake male and female mice with repeating noise burst stimuli while recording single-unit activity from primary AC. We identified parvalbumin and somatostatin interneurons through optotagging, and also separated narrow-spiking from broad-spiking units. We found that offset responses are typically less depressive than onset responses, and this result was robust to a variety of stimulus parameters, controls, measurement ty...