Traumatic brain injury (TBI) results in disrupted brain function following impact from an external force and is a risk factor for sporadic Alzheimer’s Disease (AD). Though neurological symptoms triggered by mild traumatic brain injuries (mTBI) – the most common form of TBI – typically resolve rapidly, even an isolated mTBI event can increase the risk to develop AD. Aberrant accumulation of amyloid beta peptide (Aβ), a cleaved fragment of amyloid precursor protein (APP), is a key pathological outcome designating the progression of AD following mTBI and has also been linked to impaired axonal transport. However, relationships among mTBI, amyloidogenesis, and axonal transport remain unclear, in part due to the dearth of human models to study the neuronal response following mTBI. Here, we implemented a custom-microfabricated device to deform neurons derived from human induced pluripotent stem cells (hiPSC), derived from a cognitively unimpaired male individual, to mimic the mild stretch experienced by neurons ...

We tested how a stimulus gestalt, defined by the neuronal interaction between local and global features of a stimulus, is represented within human primary visual cortex (V1). We used high-resolution functional magnetic resonance imaging (fMRI), which serves as a surrogate of neuronal activation, to measure co-fluctuations within sub-regions of V1 as (male and female) subjects were presented with peripheral stimuli, each with different global configurations. We found stronger cross-hemisphere correlations when fine-scale V1 cortical sub-regions represented parts of the same object, as compared to different objects. This result was consistent with the vertical bias in global processing and, critically, was independent of the task and local discontinuities within objects. Thus, despite the relatively small receptive fields of neurons within V1, global stimulus configuration affects neuronal processing via correlated fluctuations between regions that represent different sectors of the visual field. SIGNIFICAN...

It has been proposed that the auditory cortex in the deaf humans might undergo task-specific reorganization. However, evidence remains scarce as previous experiments used only two very specific tasks (temporal processing and face perception) in visual modality. Here, congenitally deaf/hard of hearing and hearing women and men were enrolled in an fMRI experiment as we sought to fill this evidence gap in two ways. First, we compared activation evoked by a temporal processing task performed in two different modalities: visual and tactile. Second, we contrasted this task with a perceptually similar task that focuses on the spatial dimension. Additional control conditions consisted of passive stimulus observation. In line with the task-specificity hypothesis, the auditory cortex in the deaf was activated by temporal processing in both visual and tactile modalities. This effect was selective for temporal processing relative to spatial discrimination. However, spatial processing also led to significant auditory ...

Gamma band plays a key role in the encoding of visual features in the primary visual cortex (V1). In rodents V1 two ranges within the gamma band are sensitive to contrast: a broad gamma band (BB) increasing with contrast, and a narrow gamma band (NB), peaking at ⁓60 Hz, decreasing with contrast. The functional roles of the two bands and the neural circuits originating them are not completely clear yet. Here we show, combining experimental and simulated data, that in mice V1 i) BB carries information about high contrast and NB about low contrast; ii) BB modulation depends on excitatory-inhibitory interplay in the cortex, while NB modulation is due to entrainment to the thalamic drive. In awake mice presented with alternating gratings, NB power progressively decreased from low to intermediate levels of contrast where it reached a plateau. Conversely, BB power was constant across low levels of contrast, but it progressively increased from intermediate to high levels of contrast. Furthermore, BB response was s...

Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. High frequency firing of hypothalamic arcuate Kiss1 (Kiss1ARH) neurons releases kisspeptin into the median eminence, and neurokinin B (NKB) and dynorphin onto neighboring Kiss1ARH neurons to generate a slow excitatory postsynaptic potential (EPSP) mediated by TRPC5 channels that entrains intermittent, synchronous firing of Kiss1ARH neurons. High frequency optogenetic stimulation of Kiss1ARH neurons also releases glutamate to excite the anorexigenic proopiomelanocortin (POMC) neurons and inhibit the orexigenic neuropeptide Y/agouti-related peptide (AgRP) neurons via metabotropic glutamate receptors. At the molecular level, the endoplasmic reticulum calcium-sensing protein stromal interaction molecule 1 (STIM1) is critically involved in the regulation of neuronal Ca2+ signaling and neuronal excitability through its interaction with plasma membrane calcium...

The subgenual (sgACC) and pregenual (pgACC) anterior cingulate are important afferents of the amygdala, with different cytoarchitecture, connectivity, and function. The sgACC is associated with arousal mechanisms linked to salient cues, while the pgACC is engaged in conflict decision-making, including in social contexts. After placing same-size, small volume tracer injections into sgACC and pgACC of the same hemisphere in male Macaques, we examined anterogradely labeled fiber distribution to understand how these different functional systems communicate in the main amygdala nuclei at both mesocopic and cellular levels. The sgACC has broad-based termination patterns. In contrast, the pgACC has a more restricted pattern which was always nested in sgACC terminals. Terminal overlap occurred in subregions of the accessory basal and basal nuclei, which we termed 'hotspots'. In triple-labeling confocal studies, the majority of randomly selected CAMKIIα (+) cells (putative amygdala glutamatergic neurons) in 'hotspo...

Animals perform a series of actions in a fixed order during ritualistic innate behaviors. Although command neurons and sensory pathways responding to external stimuli that trigger these behaviors have been identified, how each action is induced in a fixed order in response to multimodal sensory stimuli remains unclear. Here, the sexually dimorphic lateral antennal lobe tract projection neuron 4 (lPN4) in male Drosophila melanogaster mediates the expression of a fixed behavioral action pattern at the beginning of the courtship ritual, in which a male taps a female body and then extends a wing unilaterally to produce a courtship song. We found that blocking the synaptic output of lPN4 caused an increase in the ratio of male flies that extended a wing unilaterally without tapping the female body, whereas excitation of lPN4 suppressed the transition from the tapping phase to the unilateral wing extension phase. Real-time calcium imaging showed that lPN4 is activated by a volatile pheromone, palmitoleic acid, w...

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...

The effective development of novel therapies in mouse models of neurologic disorders relies on behavioral assessments that provide accurate read-outs of neuronal dysfunction and/or degeneration. We designed an automated behavioral testing system (PiPaw), which integrates an operant lever-pulling task directly into the mouse home cage. This task is accessible to group-housed mice 24 h per day, enabling high-throughput longitudinal analysis of forelimb motor learning. Moreover, this design eliminates the need for exposure to novel environments and minimizes experimenter interaction, significantly reducing two of the largest stressors associated with animal behavior. Male mice improved their performance of this task over 1 week of testing by reducing intertrial variability of reward-related kinematic parameters (pull amplitude or peak velocity). In addition, mice displayed short-term improvements in reward rate, and a concomitant decrease in movement variability, over the course of brief bouts of task engagem...

In the vertebrate CNS, oligodendrocytes produce myelin, a specialized membrane, to insulate and support axons. Individual oligodendrocytes wrap multiple axons with myelin sheaths of variable lengths and thicknesses. Myelin grows at the distal ends of oligodendrocyte processes, and multiple lines of work have provided evidence that mRNAs and RNA binding proteins localize to myelin, together supporting a model where local translation controls myelin sheath growth. What signal transduction mechanisms could control this? One strong candidate is the Akt-mTOR pathway, a major cellular signaling hub that coordinates transcription, translation, metabolism, and cytoskeletal organization. Here, using zebrafish as a model system, we found that Akt-mTOR signaling promotes myelin sheath growth and stability during development. Through cell-specific manipulations to oligodendrocytes, we show that the Akt-mTOR pathway drives cap-dependent translation to promote myelination and that restoration of cap-dependent translatio...