Astrocytes are essential for the formation and maintenance of neural networks. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Despite recent advances in human pluripotent stem cell (hPSC) techniques, primary rodent astrocytes remain the gold standard in coculture with human neurons. We demonstrate that a combination of leukemia inhibitory factor (LIF) and bone morphogenetic protein-4 (BMP4) directs hPSC-derived neural precursor cells to a highly pure population of astroglia in 28 d. Using single-cell RNA sequencing, we confirm the astroglial identity of these cells and highlight profound transcriptional adaptations in cocultured hPSC-derived astrocytes and neurons, consistent with their further maturation. In coculture with human neurons, multielectrode array recordings revealed robust network activity of human neurons in a coculture with hPSC-derived or rat astrocytes [3.63 ± ...

Contemporary research has begun to show a strong relationship between movements and the perception of time. More specifically, concurrent movements serve to both bias and enhance time estimates. To explain these effects, we recently proposed a mechanism by which movements provide a secondary channel for estimating duration that is combined optimally with sensory estimates. However, a critical test of this framework is that by introducing “noise” into movements, sensory estimates of time should similarly become noisier. To accomplish this, we had human participants move a robotic arm while estimating intervals of time in either auditory or visual modalities ( n = 24, ea.). Crucially, we introduced an artificial “tremor” in the arm while subjects were moving, that varied across three levels of amplitude (1–3 N) or frequency (4–12 Hz). The results of both experiments revealed that increasing the frequency of the tremor led to noisier estimates of duration. Further, the effect of noise varied with the base pre...

Studies employing EEG to measure somatosensory responses have been typically optimized to compute event-related potentials in response to discrete events. However, tactile interactions involve continuous processing of nonstationary inputs that change in location, duration, and intensity. To fill this gap, this study aims to demonstrate the possibility of measuring the neural tracking of continuous and unpredictable tactile information. Twenty-seven young adults (females, 15) were continuously and passively stimulated with a random series of gentle brushes on single fingers of each hand, which were covered from view. Thus, tactile stimulations were unique for each participant and stimulated fingers. An encoding model measured the degree of synchronization between brain activity and continuous tactile input, generating a temporal response function (TRF). Brain topographies associated with the encoding of each finger stimulation showed a contralateral response at central sensors starting at 50 ms and peaking ...

In the article “The Lack of Synapsin Alters Presynaptic Plasticity at Hippocampal Mossy Fibers in Male Mice” by Felicitas Bruentgens, Laura Moreno Velasquez, Alexander Stumpf, Daniel Parthier, Jörg Breustedt, Fabio Benfenati, Dragomir Milovanovic, …

Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the MeCP2 gene, is characterized by cognitive and social deficits. Previous studies have noted hypoactivity in the medial prefrontal cortex (mPFC) pyramidal neurons of MeCP2-deficient mice (RTT mice) in response to both social and nonsocial stimuli. To further understand the neural mechanisms behind the social deficits of RTT mice, we monitored excitatory pyramidal neurons in the prelimbic region of the mPFC during social interactions in mice. These neurons’ activity was closely linked to social preference, especially in wild-type mice. However, RTT mice showed reduced social interest and corresponding hypoactivity in these neurons, indicating that impaired mPFC activity contributes to their social deficits. We identified six mPFC neural ensembles selectively tuned to various stimuli, with RTT mice recruiting fewer neurons to ensembles responsive to social interactions and consistently showing lower stimulus-ON ensemble transi...

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.) ...