Most models of neural responses are constructed to reproduce the average response to inputs but lack the flexibility to capture observed variability in responses. The origins and structure of this variability have significant implications for how information is encoded and processed in the nervous system, both by limiting information that can be conveyed and by determining processing strategies that are favorable for minimizing its negative effects. Here, we present a new modeling framework that incorporates multiple sources of noise to better capture observed features of neural response variability across stimulus conditions. We apply this model to retinal ganglion cells at two different ambient light levels and demonstrate that it captures the full distribution of responses. Further, the model reveals light level-dependent changes that could not be seen with previous models, showing both large changes in rectification of nonlinear circuit elements and systematic differences in the contributions of differ...

Generalization of sensorimotor adaptation across limbs, known as interlimb transfer, is a well-demonstrated phenomenon in humans, yet the underlying neural mechanisms remain unclear. Theoretical models suggest that interlimb transfer is mediated by interhemispheric transfer of information via the corpus callosum. We thus hypothesized that lesions of the corpus callosum, especially to its midbody connecting motor, supplementary motor, and premotor areas of the two cerebral hemispheres, would impair interlimb transfer of sensorimotor adaptation. To test this hypothesis, we recruited three patients: two rare stroke patients with recent, extensive callosal lesions including the midbody and one patient with complete agenesis. A prismatic adaptation paradigm involving unconstrained arm reaching movements was designed to assess interlimb transfer from the prism-exposed dominant arm (DA) to the unexposed non-dominant arm (NDA) for each participant. Baseline results showed that spatial performance of each patient d...

Congenital sensorineural hearing loss (SNHL) affects thousands of infants each year and results in significant delays in speech and language development. Previous studies have shown that early exposure to a simple augmented acoustic environment (AAE) can limit the effects of progressive SNHL on hearing sensitivity. However, SNHL is also accompanied by hearing loss that is not assessed on standard audiological examinations, such as reduced temporal processing acuity. To assess whether sound therapy may improve these deficits, a mouse model of congenital SNHL was exposed to simple or temporally complex AAE. The DBA/2J mouse strain develops rapid, base to apex, progressive SNHL beginning at birth and is functionally deaf by six months of age. Hearing sensitivity and auditory brainstem function was measured using otoacoustic emissions, auditory brainstem response (ABR) and extracellular recording from the inferior colliculus (IC) in mice following exposure to 30 d of continuous AAE. Peripheral function and sou...

Depth sensitivity has been shown to be modulated by object context (plausibility). It is possible that it is behavioral relevance rather than object plausibility per se which drives this effect. Here, we manipulated the biological relevance of objects (face or a non-face) and tested whether object relevance affects behavioral sensitivity and neural responses to depth-position. In a first experiment, we presented human observers with disparity-defined faces and non-faces, and observers were asked to judge the depth position of the target under signal-noise and clear (fine) task conditions. In the second experiment, we concurrently measured behavioral and fMRI responses to depth. We found that behavioral performance varied across stimulus conditions such that they were significantly worse for the upright face than the inverted face and the random shape in the signal-to-noise (SNR) task, but worse for the random shape than the upright face in the feature task. Pattern analysis of fMRI responses revealed that ...

Mammalian orienting behavior consists of coordinated movements of the eyes, head, pinnae, vibrissae, or body to attend to an external stimulus. The present study aimed to develop a novel operant task using a touch-screen system to measure spatial attention. In this task, rats were trained to nose-poke a light stimulus presented in one of three locations. The stimulus was presented more frequently in the center location to develop spatial attention bias toward the center stimulus. Changes in orienting responses were detected by measuring the animals’ response accuracy and latency to stimuli at the lateral locations, following reversible unilateral chemogenetic inactivation of the superior colliculus (SC). Additionally, spontaneous turning and rotation behavior was measured using an open-field test (OFT). Our results show that right SC inactivation significantly increased the whole body turn angle in the OFT, in line with previous literature that indicated an ipsiversive orientating bias and the presence of ...

Our lives unfold as sequences of events. We experience these events as seamless, although they are composed of individual images captured in between the interruptions imposed by eye blinks and saccades. Events typically involve visual imagery from the real world (scenes), and the hippocampus is frequently engaged in this context. It is unclear, however, whether the hippocampus would be similarly responsive to unfolding events that involve abstract imagery. Addressing this issue could provide insights into the nature of its contribution to event processing, with relevance for theories of hippocampal function. Consequently, during magnetoencephalography (MEG), we had female and male humans watch highly matched unfolding movie events composed of either scene image frames that reflected the real world, or frames depicting abstract patterns. We examined the evoked neuronal responses to each image frame along the time course of the movie events. Only one difference between the two conditions was evident, and tha...

Stereotaxic access to brain areas underneath the superior sagittal sinus (SSS) is notoriously challenging. As a major drainage vessel, covering the whole extension of the sagittal fissure, the SSS impedes direct bilateral access to underlying regions for recording and stimulation probes, drug-delivery cannulas, and injection devices. We now describe a new method for transection and retraction of the SSS in rats, that allows the accurate placement of microinjection devices, or chronic electrode probes, while avoiding hemorrhage and the ensuing deleterious consequences for local structures, animal health, and behavior. To demonstrate the feasibility of this approach we evaluated its consequences acutely during surgery, and thereafter during surgical survival, recovery, behavioral testing, as well as postmortem analysis of histologic impact in the related brain structures of male rats. This method provides a new approach enabling direct access for manipulation and recording of activity in brain areas previous...

Developmental nicotine exposure (DNE), alters brainstem neurons that control breathing, including hypoglossal motor neurons (XIIMNs), which innervate the tongue. Here, we tested the hypothesis that chronic, episodic DNE (eDNE), which mimics nicotine replacement therapies such as e-cigarettes or nicotine gum, alters the function of nicotinic acetylcholine receptors (nAChRs), XIIMN intrinsic properties, and tongue muscle function in vivo similar to what we have observed with a chronic, sustained exposure model. We delivered nicotine to pregnant Sprague Dawley rats through drinking water and studied pups of either sex in two age groups: postnatal day (P)1–P5 and P10–P12, which encompasses a critical period in brain development. At P1–P5, eDNE was associated with delayed recovery of nAChRs from desensitization; however, there were no changes in the magnitude of desensitization, XIIMN intrinsic properties, or tongue muscle function in vivo. By P10–P12, eDNE XIIMNs had lower peak firing frequencies in response t...

There is molecular, electrophysiological, and ultrastructural evidence that a net increase in synaptic strength occurs in many brain circuits during spontaneous wake (SW) or short sleep deprivation, reflecting ongoing learning. Sleep leads instead to a broad but selective weakening of many forebrain synapses, thus preventing synaptic saturation and decreasing the energy cost of synaptic activity. Whether synaptic potentiation can persist or further increase after long sleep deprivation is unknown. Whether synaptic renormalization can occur during chronic sleep restriction (CSR) is also unknown. Here, we addressed these questions by measuring an established ultrastructural measure of synaptic strength, the axon-spine interface (ASI), in the primary motor cortex (M1) of (1) one-month-old adolescent mice CSR using a paradigm that decreases NREM and REM sleep by two/thirds; (2) in two-week-old mouse pups sleep deprived for 15 h, or allowed afterward to recover for 16 h. Both groups were compared with mice of t...

Sleep spindles, bursts of electroencephalogram (EEG) activity in the σ-frequency (11–16 Hz) range, may be biomarkers of cortical development. Studies capturing the transition to adolescence are needed to delineate age-related, sex-related, and pubertal-related changes in sleep spindles at the population-level. We analyzed the sleep EEG of 572 subjects 6–21 years (48% female) and 332 subjects 5–12 years (46% female) followed-up at 12–22 years. From 6 to 21 years, spindle density ( p quadratic = 0.019) and fast (12–16 Hz) spindle percent ( p quadratic = 0.016) showed inverted U-shaped trajectories, with plateaus after 15 and 19 years, respectively. Spindle frequency increased ( p linear < 0.001), while spindle power decreased ( p linear < 0.001) from 6 to 21 years. The trajectories of spindle density, frequency, and fast spindle percent diverged between females and males, in whom density plateaued by 14 years, fast spindle percent by 16 years, and frequency by 18 years, while fast spindle percent and spindle...