Episodic memory is a recollection of past personal experiences associated with particular times and places. This kind of memory is commonly subject to loss of contextual information or “semantization,” which gradually decouples the encoded memory items from their associated contexts while transforming them into semantic or gist-like representations. Novel extensions to the classical Remember/Know (R/K) behavioral paradigm attribute the loss of episodicity to multiple exposures of an item in different contexts. Despite recent advancements explaining semantization at a behavioral level, the underlying neural mechanisms remain poorly understood. In this study, we suggest and evaluate a novel hypothesis proposing that Bayesian–Hebbian synaptic plasticity mechanisms might cause semantization of episodic memory. We implement a cortical spiking neural network model with a Bayesian–Hebbian learning rule called Bayesian Confidence Propagation Neural Network (BCPNN), which captures the semantization phenomenon and o...

Transcranial magnetic stimulation (TMS) is widely used for understanding brain function in neurologically intact subjects and for the treatment of various disorders. However, the precise neurophysiological effects of TMS at the site of stimulation remain poorly understood. The local effects of TMS can be studied using concurrent TMS-functional magnetic resonance imaging (fMRI), a technique where TMS is delivered during fMRI scanning. However, although concurrent TMS-fMRI was developed over 20 years ago and dozens of studies have used this technique, there is still no consensus on whether TMS increases blood oxygen level-dependent (BOLD) activity at the site of stimulation. To address this question, here we review all previous concurrent TMS-fMRI studies that reported analyses of BOLD activity at the target location. We find evidence that TMS increases local BOLD activity when stimulating the primary motor (M1) and visual (V1) cortices but that these effects are likely driven by the downstream consequences ...

The primary sensory modality for probing spatial orientation can vary among psychophysical tasks. In the subjective visual vertical (SVV) task, a visual stimulus is used to measure perceived vertical orientation, while a haptic stimulus is used in the subjective haptic vertical (SHV) task. Here we examined disparity in SHV and SVV task results and asked whether it could be related to biases in probing different spatial estimates by each task. Forty-two healthy volunteers (mean ± SD age, 25 ± 10 years; 19 females; 21 left handed) were recruited. The effect of a task to measure spatial orientation was calculated as the difference between SHV and SVV values, and with the head upright and tilted 20° laterally. There was a task bias regardless of head position related to hand use in the haptic task but not handedness (mean head upright ± SEM: left hand, −3.7 ± 1.1°; right hand, 7.9 ± 1.0°). When this task bias was subtracted out, there was a similar spatial bias using each hand in the SHV task that was also com...

Estrogen plays fundamental roles in nervous system development and function. Traditional studies examining the effect of estrogen in the brain have focused on the nuclear estrogen receptors (ERs), ERα and ERβ. Studies related to the extranuclear, membrane-bound G-protein-coupled ER (GPER/GPR30) have revealed a neuroprotective role for GPER in mature neurons. In this study, we investigated the differential effects of GPER activation in primary rat embryonic day 18 (E18) hippocampal and cortical neurons. Microscopy imaging, multielectrode array (MEA), and Ca2+ imaging experiments revealed that GPER activation with selective agonist, G-1, and nonselective agonist, 17β-estradiol (E2), increased neural growth, neural firing activity, and intracellular Ca2+ more profoundly in hippocampal neurons than in cortical neurons. The GPER-mediated Ca2+ rise in hippocampal neurons involves internal Ca2+ store release via activation of phospholipase C (PLC) and extracellular entry via Ca2+ channels. Immunocytochemistry res...

X-linked dystonia-parkinsonism (XDP) is an inherited, X-linked, adult-onset movement disorder characterized by degeneration in the neostriatum. No therapeutics alter disease progression. The mechanisms underlying regional differences in degeneration and adult onset are unknown. Developing therapeutics requires a deeper understanding of how XDP-relevant features vary in health and disease. XDP is possibly due, in part, to a partial loss of TAF1 function. A disease-specific SINE-VNTR-Alu (SVA) retrotransposon insertion occurs within intron 32 of TAF1 , a subunit of TFIID involved in transcription initiation. While all XDP males are usually clinically affected, females are heterozygous carriers generally not manifesting the full syndrome. As a resource for disease modeling, we characterized eight iPSC lines from three XDP female carrier individuals for X chromosome inactivation (XCI) status and identified clonal lines that express either the wild-type X or XDP haplotype. Furthermore, we characterized XDP-rele...

Recent studies using intracellular recordings in awake behaving mice revealed that cortical network states, defined based on membrane potential features, modulate sensory responses and perceptual outcomes. Single-cell intracellular recordings are difficult and have low yield compared to extracellular recordings of population signals, such as local field potentials (LFPs). However, it is currently unclear how to identify these behaviorally-relevant network states from the LFP. We used simultaneous LFP and intracellular recordings in the somatosensory cortex of awake mice to design a network state classification from the LFP, the Network State Index (NSI). We used the NSI to analyze the relationship between single-cell (intracellular) and population (LFP) signals over different network states of wakefulness. We found that graded levels of population signal faithfully predicted the levels of single-cell depolarization in nonrhythmic regimes whereas, in δ ([2–4 Hz]) oscillatory regimes, the graded levels of rh...

The entopeduncular nucleus (EPN) and substantia nigra pars reticulata (SNr) constitute the output nuclei of the basal ganglia, but studies on the EPN are limited compared with those on the SNr. Both nuclei receive projections from the striatum with axons containing substance P (SP) and cannabinoid type-1 receptor (CB1R), and immunoreactivities for these substances show complementary patterns in the striatum and SNr. In this study, we revealed a similar complementarity in the mouse EPN, combined it with region-specific neuronal distributions, and defined subregions of the EPN. First, the EPN was divided into two areas, one showing low SP and high CB1R (lSP/hCB1R) immunoreactivities, and the other showing high SP and low CB1R (hSP/lCB1R). The former received inputs from the dorsolateral striatum that are innervated by sensorimotor cortices, whereas the latter received inputs from the medial striatum that are innervated by limbic/association cortices. Then, the lSP/hCB1R area was further divided into the dors...

We mourn the loss of Hirsh Cohen who died on December 20, 2020, at the age of 95. Many of us benefitted from Hirsh’s humor and wisdom, as he fostered the early growth and well being of the field of computational neuroscience. When we first met Hirsh, he was just starting his second full career, as a grant officer at the Sloan Foundation. (In his first career, Hirsh was an applied mathematician in academia and at the IBM Research Laboratory). In 1994, the field of computational neuroscience was small, and …

In the article, “Histochemical Characterization of the Dorsal Raphe-Periaqueductal Grey Dopamine Transporter Neurons Projecting to the Extended Amygdala,” by Qin Zhao, Tetsufumi Ito, Chika Soko, Yoshie Hori, Takafumi Furuyama, Hiroyuki Hioki, Kohtarou …

Replicability, the degree to which a previous scientific finding can be repeated in a distinct set of data, has been considered an integral component of institutionalized scientific practice since its inception several hundred years ago. In the past decade, large-scale replication studies have demonstrated that replicability is far from favorable, across multiple scientific fields. Here, I evaluate this literature and describe contributing factors including the prevalence of questionable research practices (QRPs), misunderstanding of p -values, and low statistical power. I subsequently discuss how these issues manifest specifically in preclinical neuroscience research. I conclude that these problems are multifaceted and difficult to solve, relying on the actions of early and late career researchers, funding sources, academic publishers, and others. I assert that any viable solution to the problem of substandard replicability must include changing academic incentives, with adoption of registered reports bei...