Axon regeneration after spinal cord injury (SCI) is limited by both a decreased intrinsic ability of neurons to grow axons and the growth-hindering effects of extrinsic inhibitory molecules expressed around the lesion. Deletion of phosphatase and tensin homolog ( Pten ) augments mTOR signaling and enhances the intrinsic regenerative response of injured corticospinal neurons after SCI. Due to the variety of growth-restrictive extrinsic molecules, it remains unclear how inhibition of conserved inhibitory signaling elements would affect axon regeneration and rewiring after SCI. Moreover, it remains unknown how a combinatorial approach to modulate both extrinsic and intrinsic mechanisms can enhance regeneration and rewiring after SCI. In the present study, we deleted RhoA and RhoC, which encode small GTPases that mediate growth inhibition signals of a variety of extrinsic molecules, to remove global extrinsic pathways. RhoA / RhoC double deletion in mice suppressed retraction or dieback of corticospinal axons ...

The primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input from the body periphery and external environment during ongoing movement. Mouse S1 consists of several distinct sensorimotor subnetworks that receive topographically organized corticocortical inputs from distant sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major long-range inputs to this S1 area. Silencing S2→non-whisker S1 projections alters the hind paw orientation during locomotion, whereas manipulation of the M1 projection has litt...

The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts in vivo . We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution. At the individual subject level, we identified the lateral, medial, and intermediate striae with their respecti...

Detection of statistical irregularities, measured as a prediction error response, is fundamental to the perceptual monitoring of the environment. We studied whether prediction error response is associated with neural oscillations or asynchronous broadband activity. Electrocorticography was conducted in three male monkeys, who passively listened to the auditory roving oddball stimuli. Local field potentials (LFPs) recorded over the auditory cortex underwent spectral principal component analysis, which decoupled broadband and rhythmic components of the LFP signal. We found that the broadband component captured the prediction error response, whereas none of the rhythmic components were associated with statistical irregularities of sounds. The broadband component displayed more stochastic, asymmetrical multifractal properties than the rhythmic components, which revealed more self-similar dynamics. We thus conclude that the prediction error response is captured by neuronal populations generating asynchronous br...

Parvalbumin-containing (PV+) basket cells are specialized cortical interneurons that regulate the activity of local neuronal circuits with high temporal precision and reliability. To understand how the PV+ interneuron connectivity underlying these functional properties is established during development, we used array tomography to map pairs of synaptically connected PV+ interneurons and postsynaptic neurons from the neocortex of mice of both sexes. We focused on the axon-myelin unit of the PV+ interneuron and quantified the number of synapses onto the postsynaptic neuron, length of connecting axonal paths, and their myelination at different time points between 2 weeks and 7 months of age. We find that myelination of the proximal axon occurs very rapidly during the third and, to a lesser extent, fourth postnatal weeks. The number of synaptic contacts made by the PV+ interneuron on its postsynaptic partner meanwhile is significantly reduced to about one-third by the end of the first postnatal month. The numb...

The neuronal and genetic bases of sleep, a phenomenon considered crucial for well-being of organisms, has been under investigation using the model organism Drosophila melanogaster . Although sleep is a state where sensory threshold for arousal is greater, it is known that certain kinds of repetitive sensory stimuli, such as rocking, can indeed promote sleep in humans. Here we report that orbital motion-aided mechanosensory stimulation promotes sleep of male and female Drosophila , independent of the circadian clock, but controlled by the homeostatic system. Mechanosensory receptor nanchung ( Nan )-expressing neurons in the chordotonal organs mediate this sleep induction: flies in which these neurons are either silenced or ablated display significantly reduced sleep induction on mechanosensory stimulation. Transient activation of the Nan -expressing neurons also enhances sleep levels, confirming the role of these neurons in sleep induction. We also reveal that certain regions of the antennal mechanosensory ...

Amygdala abnormalities characterize several psychiatric disorders with prominent social deficits and often emerge during adolescence. The basolateral amygdala (BLA) bidirectionally modulates social behavior and has increased sensitivity during adolescence. We tested how an environmentally-driven social state is regulated by the BLA in adults and adolescent male rats. We found that a high social drive state caused by brief social isolation increases age-specific social behaviors and increased BLA neuronal activity. Chemogenetic inactivation of BLA decreased the effect of high social drive on social engagement. High social drive preferentially enhanced BLA activity during social engagement; however, the effect of social opportunity on BLA activity was greater during adolescence. While this identifies a substrate underlying age differences in social drive, we then determined that high social drive increased BLA NMDA GluN2B expression and sensitivity to antagonism increased with age. Further, the effect of a h...

Human behavior is biased by past experience. For example, when intercepting a moving target, the speed of previous targets will bias responses in future trials. Neural mechanisms underlying this so-called serial dependence are still under debate. Here, we tested the hypothesis that the previous trial leaves a neural trace in brain regions associated with encoding task-relevant information in visual and/or motor regions. We reasoned that injecting noise by means of transcranial magnetic stimulation (TMS) over premotor and visual areas would degrade such memory traces and hence reduce serial dependence. To test this hypothesis, we applied bursts of TMS pulses to right visual motion processing region hV5/MT+ and to left dorsal premotor cortex (PMd) during intertrial intervals of a coincident timing task performed by twenty healthy human participants (15 female). Without TMS, participants presented a bias toward the speed of the previous trial when intercepting moving targets. TMS over PMd decreased serial dep...

The exquisite capacity of primates to detect and recognize faces is crucial for social interactions. Although disentangling the neural basis of human face recognition remains a key goal in neuroscience, direct evidence at the single-neuron level is limited. We recorded from face-selective neurons in human visual cortex in a region characterized by functional magnetic resonance imaging (fMRI) activations for faces compared with objects. The majority of visually responsive neurons in this fMRI activation showed strong selectivity at short latencies for faces compared with objects. Feature-scrambled faces and face-like objects could also drive these neurons, suggesting that this region is not tightly tuned to the visual attributes that typically define whole human faces. These single-cell recordings within the human face processing system provide vital experimental evidence linking previous imaging studies in humans and invasive studies in animal models. SIGNIFICANCE STATEMENT We present the first recordings...