Previous physiological and psychophysical studies have explored whether feedback to the cochlea from the efferent system influences forward masking. The present work proposes that the limited growth-of-masking (GOM) observed in auditory nerve (AN) fibers may have been misunderstood; namely, that this limitation may be due to the influence of anesthesia on the efferent system. Building on the premise that the unanesthetized AN may exhibit GOM similar to more central nuclei, the present computational modeling study demonstrates that feedback from the medial olivocochlear (MOC) efferents may contribute to GOM observed physiologically in onset-type neurons in both the cochlear nucleus and inferior colliculus (IC). Additionally, the computational model of MOC efferents used here generates a decrease in masking with longer masker-signal delays similar to that observed in IC physiology and in psychophysical studies. An advantage of this explanation over alternative physiological explanations (e.g., that forward m...

Much of what has been discovered concerning neurophysiological mechanisms can be credited to ex vivo biomedical experiments. Beyond these discoveries, ex vivo research techniques have enhanced the global understanding of human physiology and pathology in almost every biomedical specialty. Naturally, ex vivo experiments are among the most desired methods of research, particularly in the field of neuroscience. Ex vivo experiment platforms may be purchased commercially. However, their substantial cost and sometimes limited availability can render them inaccessible to many research labs. Moreover, these manufactured systems are often rigid in function with no possibility of customization, severely narrowing their capabilities. However, developing essential components for ex vivo laboratory systems with a fused deposition modeling printer provides a practical solution to each of these obstacles. Here, we provide the designs and construction process for an easily accessible, highly adaptable recording stage with...

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...

Generalized epilepsy (GE) encompasses a heterogeneous group of hyperexcitability disorders that clinically manifest as seizures. At the whole-brain level, distinct seizure patterns as well as interictal epileptic discharges (IEDs) reflect key signatures of hyperexcitability in magneto- and electroencephalographic (M/EEG) recordings. Moreover, it had been suggested that aperiodic activity, specifically the slope of the 1/ ƒx decay function of the power spectrum, might index neural excitability. However, it remained unclear if hyperexcitability as encountered at the cellular level directly translates to putative large-scale excitability signatures, amenable to M/EEG. In order to test whether the power spectrum is altered in hyperexcitable states, we recorded resting-state MEG from male and female GE patients ( n  = 51; 29 females; 28.82 ± 12.18 years; mean ± SD) and age-matched healthy controls ( n  = 49; 22 females; 32.10 ± 12.09 years). We parametrized the power spectra using FOOOF (“fitting oscillations a...

Chemotherapy-related cognitive impairments (CRCIs) encompass cognitive deficits in memory, attention, and executive function that arise during and following chemotherapy. CRCI symptoms are predominantly reported by female cancer patients but also occur in males. These impairments may involve reduced estradiol levels, which then increases vulnerability to the impact of tumors and chemotherapy on cognition. This study utilized the MMTV-PyVT mouse model of breast cancer to test the hypothesis that impaired ovarian function and associated estradiol levels play a critical role in CRCI susceptibility. Mice were either ovariectomized (OVX) or underwent sham surgery. The OVX group then received supplemental estradiol (E2) ad libitum in the drinking water to maintain physiological hormone levels. After tumor development, mice were trained in the Morris water maze to assess spatial memory, and subsequently, they received weekly injections of either saline or a combination of cyclophosphamide (CYP; 66.7 mg/kg, i.v.) ...

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 ...

Conscious reportability of visual input is associated with a bimodal neural response in the primary visual cortex (V1): an early-latency response coupled to stimulus features and a late-latency response coupled to stimulus report or detection. This late wave of activity, central to major theories of consciousness, is thought to be driven by the prefrontal cortex (PFC), responsible for “igniting” it. Here we analyzed two electrophysiological studies in mice performing different stimulus detection tasks and characterized neural activity profiles in three key cortical regions: V1, posterior parietal cortex (PPC), and PFC. We then developed a minimal network model, constrained by known connectivity between these regions, reproducing the spatiotemporal propagation of visual- and report-related activity. Remarkably, while PFC was indeed necessary to generate report-related activity in V1, this occurred only through the mediation of PPC. PPC, and not PFC, had the final veto in enabling the report-related late wav...

Systemic inflammation has been implicated in the development and progression of neurodegenerative conditions such as cognitive impairment and dementia. Recent clinical studies indicate an association between sepsis, endothelial dysfunction, and cognitive decline. However, the investigations of the role and therapeutic potential of the cerebral microvasculature in sepsis-induced cognitive dysfunction have been limited by the lack of standardized experimental models for evaluating the alterations in the cerebral microvasculature and cognition induced by the systemic inflammatory response. Herein, we validated a mouse model of endotoxemia that recapitulates key pathophysiology related to sepsis-induced cognitive dysfunction, including the induction of an acute systemic hyperinflammatory response, blood–brain barrier (BBB) leakage, neurovascular inflammation, and memory impairment after recovery from the systemic inflammation. In the acute phase, we identified novel molecular (e.g., upregulation of plasmalemma...

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...