Sensory processing disruptions are a core symptom of autism spectrum disorder (ASD) and other neurological disorders. The acoustic startle response and prepulse inhibition (PPI) are common metrics used to assess disruptions in sensory processing and sensorimotor gating in clinical studies and animal models. However, often there are inconsistent findings on ASD-related PPI deficits across different studies. Here, we used a novel method for assessing changes in startle and PPI in rodents, using the Cntnap2 knock-out (KO) rat model for neurodevelopmental disorder/ASD that has consistently shown PPI disruptions in past studies. We discovered that not only sex and prepulse intensity but also the intensity of the startle stimulus profoundly impacts whether PPI deficits are evident in the Cntnap2 KO rat or not. We show that rats do not universally exhibit a PPI deficit; instead, impaired PPI is contingent on specific testing conditions. Notably, at lower startle stimulus intensities, Cntnap2 KO rats not only demo...

The accurate estimation of limb state is necessary for movement planning and execution. While state estimation requires both feedforward and feedback information, we focus here on the latter. Prior literature has shown that integrating visual and proprioceptive feedback improves estimates of static limb position. However, differences in visual and proprioceptive feedback delays suggest that multisensory integration could be disadvantageous when the limb is moving. We formalized this hypothesis by modeling feedback-based state estimation using the long-standing maximum likelihood estimation model of multisensory integration, which we updated to account for sensory delays. Our model predicted that the benefit of multisensory integration was largely lost when the limb was passively moving. We tested this hypothesis in a series of experiments in human subjects that compared the degree of interference created by discrepant visual or proprioceptive feedback when estimating limb position either statically at the ...

Social recognition is an essential part of social function and often promotes specific social behaviors based on prior experience. Social and defensive behaviors in particular often emerge with prior experiences of familiarity or novelty/stress, respectively. This is also commonly seen in rodents toward same-strain and interstrain conspecifics. Medial amygdala (MeA) activity guides social choice based on age and sex recognition and is sensitive to social experiences. However, little is known about whether the MeA exhibits differential responses based on strain or how this is impacted by experience. Social stress impacts posterior MeA (MeAp) function and can shift measures of social engagement. However, it is unclear how stress impacts MeAp activity and contributes to altered social behavior. The primary goal of this study in adult male Sprague Dawley rats was to determine whether prior stress experience with a different-strain (Long–Evans) rat impacts MeAp responses to same-strain and different-strain cons...

Learning to solve a new problem involves identifying the operating rules, which can be accelerated if known rules generalize in the new context. We ask how prior experience affects learning a new rule that is distinct from known rules. We examined how rats learned a new spatial navigation task after having previously learned tasks with different navigation rules. The new task differed from the previous tasks in spatial layout and navigation rule. We found that experience history did not impact overall performance. However, by examining navigation choice sequences in the new task, we found experience-dependent differences in exploration patterns during early stages of learning, as well as differences in the types of errors made during stable performance. The differences were consistent with the animals adopting experience-dependent memory strategies to discover and implement the new rule. Our results indicate prior experience shapes the strategies for solving novel problems, and the impact of prior experien...

Contrast sensitivity (CS), which constrains human vision, decreases from fovea to periphery, from the horizontal to the vertical meridian, and from the lower vertical to the upper vertical meridian. It also depends on spatial frequency (SF), and the contrast sensitivity function (CSF) depicts this relation. To compensate for these visual constraints, we constantly make saccades and foveate on relevant objects in the scene. Already before saccade onset, presaccadic attention shifts to the saccade target and enhances perception. However, it is unknown whether and how it modulates the interplay between CS and SF, and if this effect varies around polar angle meridians. CS enhancement may result from a horizontal or vertical shift of the CSF, increase in bandwidth, or any combination. In addition, presaccadic attention could enhance CS similarly around the visual field, or it could benefit perception more at locations with poorer performance (i.e., vertical meridian). Here, we investigated these possibilities b...

Ca2+-binding proteins (CaBPs; CaBP1–5) are a subfamily of neuronal Ca2+ sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons. In this study, we conducted a comprehensive transcript analysis using single-cell RNA sequencing datasets to investigate the gene expression profiles of CaBPs in mouse and human retinal neurons. Our findings revealed notable similarities in the overall expression patterns of CaBPs across both species. Specifically, nearly all amacrine cell, ganglion cell, and horizontal cell types exclusively expressed CaBP1. In contrast, the majority of bipolar cell types, including rod bipolar (RB) cells, expressed distinct combinations of CaBP1, CaBP2, and CaBP5, rather than a single CaBP as previ...

A multidisciplinary and international convergent working group (neural stem cell biology, functional electrical stimulation, materials engineering, electrical engineering, neurosurgery, neurology, biomedical device, and commercialization) met in Canada to create a call to action for Electrical Stimulation for Neural Repair. Electrical stimulation, in the form of deep brain stimulation (DBS), is an approved treatment for various neurological disorders such as essential tremor, Parkinson's disease, and epilepsy. Here, DBS works through disrupting neural circuits; however, electrical stimulation may also effectively promote neural repair due to the activation of electrosensitive resident neural stem cells. Activating neural stem cells has great promise for enhancing neuroplasticity to treat damaged brains. To realize this therapy's potential, multidisciplinary experts met to identify barriers, gaps, and next steps. Neurological disorders are a leading cause of death and disabilities worldwide and represent a...

The goal of connectomics is to reveal the links between neural circuits and behavior. Larvae of the primitive chordate Ciona are well-suited to make contributions in this area. In addition to having a described connectome, Ciona larvae have a range of readily quantified behaviors. Moreover, the small number of neurons in the larval CNS (∼180) holds the promise of a comprehensive characterization of individual neurons. We present single-neuron predictions for glutamate receptor (GlutR) expression based on in situ hybridization. Included are both ionotropic receptors (AMPA, NMDA, and kainate) and metabotropic receptors. The predicted glutamate receptor expression dataset is discussed in the context of known circuits driving behaviors such as phototaxis, mechanosensation, and looming shadow response. The predicted expression of AMPA and NMDA receptors may help resolve issues regarding the co-production of GABA and glutamate by a subset of photoreceptors. The targets of these photoreceptors in the midbrain app...

Alteration of synaptic function in the dorsal horn (DH) has been implicated as a cellular substrate for the development of neuropathic pain, but certain details remain unclear. In particular, the lack of information on the types of synapses that undergo functional changes hinders the understanding of disease pathogenesis from a synaptic plasticity perspective. Here, we addressed this issue by using optogenetic and retrograde tracing ex vivo to selectively stimulate first-order nociceptors expressing Nav1.8 (NRsNav1.8) and record the responses of spinothalamic tract neurons in spinal lamina I (L1-STTNs). We found that spared nerve injury (SNI) increased excitatory postsynaptic currents (EPSCs) in L1-STTNs evoked by photostimulation of NRsNav1.8 (referred to as Nav1.8-STTN EPSCs). This effect was accompanied by a significant change in the failure rate and paired-pulse ratio of synaptic transmission from NRsNav1.8 to L1-STTN and in the frequency (not amplitude) of spontaneous EPSCs recorded in L1-STTNs. Howev...

When presented shortly after another, discrete pictures are naturally perceived as continuous. The neuronal mechanism underlying such continuous or discrete perception is not well understood. While continuous alpha oscillations are a candidate for orchestrating such neuronal mechanisms, recent evidence is mixed. In this study, we investigated the influence of prestimulus alpha oscillation on visual temporal perception. Specifically, we were interested in whether prestimulus alpha phase modulates neuronal and perceptual processes underlying discrete or continuous perception. Participants had to report the location of a missing object in a visual temporal integration task, while simultaneously MEG data were recorded. Using source reconstruction, we evaluated local phase effects by contrasting phase angle values between correctly and incorrectly integrated trials. Our results show a phase opposition cluster between −0.8 and −0.5 s (relative to stimulus presentation) and between 6 and 20 Hz. These momentary ph...