Early-life stressors can affect reproductive development and change responses to adult stress. We tested if resource scarcity in the form of limited bedding and nesting (LBN) from postnatal days (PND) 4 to 11 delayed sexual maturation in male and female mice and/or altered the response to an acute, layered, psychosocial stress (ALPS) in adulthood. Contrary to the hypotheses, age and mass at puberty were unaffected by the present application of LBN. Under basal conditions and after ALPS, corticosterone concentrations in males, diestrous females, and proestrous females reared in standard (STD) or LBN environments were similar. ALPS disrupts the luteinizing hormone (LH) surge in most mice when applied on the morning of proestrus; this effect was not changed by resource scarcity. In this study, the paucity of effects in the offspring may relate to a milder response of CBA dams to the paradigm. While LBN dams exited the nest more often and their offspring were smaller than STD-reared offspring on PND11, dam cor...

As rapid responders to their environments, microglia engage in functions that are mirrored by their cellular morphology. Microglia are classically thought to exhibit a ramified morphology under homeostatic conditions which switches to an ameboid form during inflammatory conditions. However, microglia display a wide spectrum of morphologies outside of this dichotomy, including rod-like, ramified, ameboid, and hypertrophic states, which have been observed across brain regions, neurodevelopmental timepoints, and various pathological contexts. We applied dimensionality reduction and clustering to consider contributions of multiple morphology measures together to define a spectrum of microglial morphological states in a mouse dataset that we used to demonstrate the utility of our toolset. Using ImageJ, we first developed a semiautomated approach to characterize 27 morphology features from hundreds to thousands of individual microglial cells in a brain region-specific manner. Within this pool of features, we def...

Reading depends on a brain region known as the “visual word form area” (VWFA) in the left ventral occipitotemporal cortex. This region's function is debated because its stimulus selectivity is not absolute, it is modulated by a variety of task demands, and it is inconsistently localized. We used fMRI to characterize the combination of sensory and cognitive factors that activate word-responsive regions that we precisely localized in 16 adult humans (4 male). We then presented three types of character strings: English words, pseudowords, and unfamiliar characters with matched visual features. Participants performed three different tasks while viewing those stimuli: detecting real words, detecting color in the characters, and detecting color in the fixation mark. There were three primary findings about the VWFA's response: (1) It preferred letter strings over unfamiliar characters even when the stimuli were ignored during the fixation task. (2) Compared with those baseline responses, engaging in the word read...

Psychotic symptoms and delusional beliefs have been linked to dopamine transmission in both healthy and clinical samples and are assumed to result at least in part from perceiving illusory patterns in noise. However, the existing literature on the role of dopamine in detecting patterns in noise is inconclusive. To address this issue, we assessed the effect of manipulating dopaminergic neurotransmission on illusory pattern perception in healthy individuals ( n  = 48, n  = 19 female) in a double-blind placebo-controlled within-subjects design (see preregistration at <https://osf.io/a4k9j/>). We predicted individuals on versus off ʟ-DOPA to be more likely to perceive illusory patterns, specifically objects in images containing only noise. Using a signal detection model, however, we found no credible evidence that ʟ-DOPA compared with placebo increased false alarm rates. Further, ʟ-DOPA did not reliably modulate measures of accuracy, discrimination sensitivity, and response bias. In all cases, Bayesian statist...

Impaired inhibition—and the resulting disruption of the brain's excitatory–inhibitory (E–I) balance—has historically been theorized to play a critical role in epileptogenesis and seizures (Treiman, 2001). This concept is supported by numerous studies showing impaired function of gamma-aminobutyric acid (GABA)-ergic function in both genetic and acquired animal models of epilepsy and in human epileptic brain tissue. Furthermore, medications that enhance GABAergic signaling have an anticonvulsant effect whereas GABA antagonists are proconvulsant. Yet, despite a large body of evidence implicating GABA in epileptogenesis and epilepsy, the direct causal role of inhibitory interneuron loss (or impairment) has remained incompletely understood. In the case of acquired models of epilepsy, such as temporal lobe epilepsy, interneuron loss is central to signature pathophysiology but occurs alongside multiple other pathological and neuroplastic changes that are also likely to influence disease progression. In the case ...

Generation of human induced pluripotent stem cell (hiPSC)-derived motor neurons (MNs) offers an unprecedented approach to modeling movement disorders such as dystonia and amyotrophic lateral sclerosis. However, achieving survival poses a significant challenge when culturing induced MNs, especially when aiming to reach late maturation stages. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we assembled two types of coculture systems: direct coculturing of neurons with astrocytes and indirect coculture using culture inserts that physically separate neurons and astrocytes. Both systems significantly enhance neuron survival. Compared with these two systems, no significant differences in neurodevelopment, maturation, and survival within 3 weeks, allowing to prepare neurons at maturation stages. Using the indirect coculture system, we obtained highly pure MNs at the late mature stage from hiPSCs. Transcriptomic studies of hiPSC-derived MNs showed a typical neurodevelopmental switch in gene ex...

Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine (VM) than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and VM, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel ( r  = 1.5 cm) versus rat dowel ( r  = 3.5 cm). EPM results indicate that CGRP alone or OVAR alone did not increase anxiety indices. However, the combination of CGRP and OVAR did elicit anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. These res...

We are fortunate to belong to a large undergraduate R1 research institution [at the time of writing, over 57,000 undergraduate students are enrolled at Texas A&M University (TAMU)]. Research is a major part of the undergraduate experience, and in fact many of our degree plans require undergraduate students to participate in at least one semester of laboratory research. As the principal investigator (PI) of a neuroscience laboratory (J.N.D.), former Associate Director for Undergraduate Research (S.M.M.), and current undergraduate researchers (P.G. and A.S.), we each have unique perspectives on the benefits of undergraduate research experiences (UREs). According to a 2007 report based on self-reported outcomes among undergraduates and their URE mentors, UREs increase interest in science, technology, engineering, and math (STEM) careers for over two-thirds of students who participate, and the large majority (88%) of students improve their understanding of how to conduct research (Russell et al., 2007). In an...

In the article “Apolipoprotein A1 Enhances Endothelial Cell Survival in an In Vitro Model of ALS,” by Svitlana Garbuzova-Davis, Alison E. Willing, and Cesario V. Borlongan, …

Preparing acute brain slices produces trauma that mimics severe penetrating brain injury. In neonatal acute brain slices, the spatiotemporal characteristics of trauma-induced calcium dynamics in neurons and its effect on network activity are relatively unknown. Using multiphoton laser scanning microscopy of the somatosensory neocortex in acute neonatal mouse brain slices (P8–12), we simultaneously imaged neuronal Ca2+ dynamics (GCaMP6s) and cytotoxicity (propidium iodide or PI) to determine the relationship between cytotoxic Ca2+ loaded neurons (GCaMP-filled) and cell viability at different depths and incubation times. PI+ cells and GCaMP-filled neurons were abundant at the surface of the slices, with an exponential decrease with depth. Regions with high PI+ cells correlated with elevated neuronal and neuropil Ca2+. The number of PI+ cells and GCaMP-filled neurons increased with prolonged incubation. GCaMP-filled neurons did not participate in stimulus-evoked or seizure-evoked network activity. Significant...