Ongoing efforts over the last 50 years have made data and methods more reproducible and transparent across the life sciences. This openness has led to transformative insights and vastly accelerated scientific progress ([Gražulis et al., 2012][1]; [Munafó et al., 2017][2]). For example, structural biology ([Bruno and Groom, 2014][3]) and genomics ([Benson et al., 2013][4]; [Porter and Hajibabaei, 2018][5]) have undertaken systematic collection and publication of protein sequences and structures over the past half century. These data, in turn, have led to scientific breakthroughs that were unthinkable when data collection first began ([Jumper et al., 2021][6]). We believe that neuroscience is poised to follow the same path, and that principles of open data and open science will transform our understanding of the nervous system in ways that are impossible to predict at the moment. New social structures supporting an active and open scientific community are essential ([Saunders, 2022][7]) to facilitate and exp...

A central mechanism of exposure-based cognitive behavioral therapy for anxiety and trauma-related disorders is fear extinction. However, the mechanisms underlying fear extinction are deficient in some individuals, leading to treatment resistance. Recent animal studies demonstrate that upon omission of the aversive, unconditioned stimulus (US) during fear extinction, dopamine (DA) neurons in the ventral tegmental area (VTA) produce a prediction error (PE)-like signal. However, whether this VTA-DA neuronal PE-like signal is altered in animals exhibiting deficient fear extinction has not been studied. Here, we used a mouse model of impaired fear extinction [129S1/SvImJ (S1) inbred mouse strain] to monitor and manipulate VTA-DA neurons during extinction. Male DAT-Cre mice backcrossed onto an S1 background (S1-DAT-Cre) exhibited impaired extinction but normal VTA-DA neuron number, as compared with BL6-DAT-Cre mice. In vivo fiber photometry showed that impaired extinction in male S1-DAT-Cre mice was associated w...

Signaling at nicotinic acetylcholine receptors (nAChRs) is vital for normal development of cerebral cortical circuits. These developing circuits are also shaped by fast-spiking (FS) inhibitory cortical neurons. While nicotinic dysfunction in FS neurons is implicated in a number of psychiatric and neurodevelopmental disorders, FS neurons are thought to not have nicotinic responses in adults. Here, we establish a timeline of FS neuron response to nicotine pre- and postsynaptically in primary somatosensory cortex in male and female rats. We found that nicotine increases the frequency of spontaneous synaptic inputs to FS neurons during the second postnatal week, and this effect persisted through development. In contrast, FS neurons in S1 had no postsynaptic responses to nicotine from as early as they can be reliably identified. This was not attributable to receptor desensitization, and we further revealed that FS neurons express abundant mRNA for several nAChR subunits, beginning early in development. To deter...

This study determined the association between the triglyceride-glucose (TyG) index–waist-to-hip ratio (TyG–WHR) and stroke. Data from the China Health and Retirement Longitudinal Study (CHARLS) were utilized from baseline in 2011 to the wave six follow-up in 2020. The CHARLS cohort was assembled using a multistage probability sampling technique. Participants were comprehensively assessed through standardized questionnaires with face-to-face interviews. A total of 4,911 patients with 2,338 males (47.6%) and 2,573 females (52.4%) were included in this analysis. A significant association between the TyG–WHR and the risk of stroke was identified utilizing a Cox proportional hazards regression model with cubic spline functions that were characterized by a nonlinear relationship. The analysis determined a threshold for the TyG–WHR at 4.635. The association between the TyG–WHR and stroke was not significant [hazard ratio (HR), 0.813; 95% CI, 0.662–0.999; p  = 0.049] to the left of the threshold. The association w...

Social animals compete for rewards to survive, yet the neural circuits underlying reward-based social competition remain unclear. The medial prefrontal cortex (mPFC) plays a key role in reward processing and social dominance, but whether its subregions contribute differently to competitions for reward remains unknown. Using c-Fos mapping in male CD1 mice, we examined reward-induced neural activation in mPFC subregions and key interconnected subcortical areas across social and nonsocial reward contexts. Noncompetitive social contexts produced global c-Fos activation relative to competitive contexts. Cross-regional correlation analyses revealed that receiving rewards in isolation involved widespread network coordination, while social contexts exhibited distinct, sparse correlation patterns. Surprisingly, social rank effects on neural activity were most pronounced during isolated reward experiences rather than during competition, with dominant mice showing increased anterior cingulate, basolateral amygdala, a...

Abrupt onsets reflexively shift covert spatial attention. Recent work demonstrated that trial-to-trial information about the probability of a peripheral onset modulated the magnitude of the attentional cueing effect (low probability > high probability). Although onsets were physically identical, pupil responses could have been modulated by information about the probability of the onset's appearance. Specifically, anticipatory constrictions may have preceded high-probability onsets. Here, we tested this hypothesis using centrally presented, luminance-matched onset-probability signals. For half the participants, vertical signaled high probability (0.8) of onset appearance, while horizontal signaled low probability (0.2). Contingencies were reversed for the other half. Participants fixated the onset-probability signal for 2,000 ms before the onset was briefly presented or omitted, in line with the signaled probability. To maintain engagement, participants completed a simple localization task. Preliminary evid...

Exposure to early life stress (ELS) can exert long-lasting impacts on emotional regulation. The corticolimbic system including the basolateral amygdala (BLA), ventral hippocampus (vHIP), and the medial prefrontal cortex (mPFC) plays a key role in fear learning. Using the limited bedding paradigm (LB), we examined the functional consequences of ELS on excitatory and inhibitory tone in the prelimbic (PL) mPFC after fear conditioning in rats. In adults, LB exposure enhanced in vivo glutamate release in the PL mPFC during fear conditioning in male, but not female offspring. In contrast, the glutamate response to fear conditioning was diminished in LB-exposed pre-adolescent males, but not females. We investigated whether reduced glutamatergic inputs and/or elevated inhibitory tone might contribute to the diminished glutamate response in the mPFC following LB in pre-adolescent male rats. Indeed, we found that LB exposure specifically increased the activation of PV, but not SST interneurons in layer V, but not la...

Emotional dysregulation is highly comorbid with sleep disturbances. Sleep is composed of unique physiological states that are reflected by conserved brain oscillations. Though the role of these state-dependent oscillations in cognitive function has been well established, less is known regarding the nature of state-dependent oscillations across brain regions that strongly contribute to emotional function. To characterize these dynamics, we recorded local field potentials simultaneously from multiple cortical and subcortical regions implicated in sleep and emotion regulation and characterized widespread patterns of spectral power and synchrony between brain regions during sleep-wake states in male and female mice. First, we showed that single brain regions encode sleep state, albeit to various degrees of accuracy. We then identified network-based classifiers of sleep based on the combination of features from all recorded brain regions. Spectral power and synchrony from brain networks allowed for automatic, a...

The progressive ratio (PR) schedule is a popular test of motivation. Despite its popularity, the PR task hinges on a low-dimensional behavioral readout—breakpoint or the maximum work requirement subjects are willing to complete before abandoning the task. Here, we show that with a simple modification, the PR task can be transformed into an optimization problem reminiscent of the patch-leaving foraging scenario, which has been analyzed extensively by behavioral ecologists, psychologists, and neuroscientists. In the PR with reset (PRR) task, male and female rats performed the PR task on one lever but could press a second lever to reset the current ratio requirement back to its lowest value at the cost of enduring a reset delay, during which both levers were retracted. Rats used the reset lever adaptively on the PRR task, and their ratio reset decisions were sensitive to the cost of the reset delay. We derived an approach for computing the optimal bout length—the number of rewards to earn before pressing the ...

Imagine yourself in a car race waiting for the traffic light to go green. Impulsivity could push you to accelerate when the light is still red. In contrast, temporally guided anticipation could lead you to accelerate at the time the light goes green. Whether these two types of early responses rely on the same or different neural processes is an open question. This question was investigated using an oculomotor task where the delay between a warning and an imperative visual stimuli was predictable. The spatial uncertainty of the “go” signal was also varied. On average, 10% of experimental trials were associated with a response before the “go” signal (“early saccade”). After the offset of the warning stimulus, the latency distribution of early saccades was bimodal, with a first mode peaking after 200 ms (1st mode saccades) and a second one starting to build-up after 375 ms (2nd mode saccades). With increasing delay duration: the number of 1st mode responses decreased whereas the number of 2nd mode responses r...