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...

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...

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...

Listening effort reflects the cognitive and motivational resources allocated to speech comprehension, particularly under challenging conditions. Visual cues are known to enhance speech perception, potentially by reducing the cognitive demands of the task. However, the neurophysiological mechanisms underlying this facilitation, especially in terms of effort-related changes, remain unclear. In this study, we combined pupillometry and electroencephalography (EEG) to investigate how visual speech cues modulate cognitive effort during speech recognition. Twenty-two participants (seven females) performed a speech-in-noise task under three modalities: (1) auditory-only, (2) audiovisual, and (3) visual-only. Task difficulty was manipulated via signal-to-noise ratio (SNR) in the first two modalities. Firstly, we found an inverted U-shape relationship between pupil dilation and frontal midline theta with SNR for audiovisual and auditory-only speech, consistent with prior models of effort allocation. Secondly, we obs...

Identifying neural signatures of slow-wave sleep (SWS) is important for a number of reasons including diagnosing potential sleep disorders and examining its role in memory consolidation ( [Diekelmann and Born, 2010][1]; [Klinzing et al., 2019][2]; [Brodt et al., 2023][3]). Studies of sleep in the common marmoset ( Callithrix jacchus ) have revealed similarities to humans and other nonhuman primates, including distinct sleep stages ( [Crofts et al., 2001][4]) and diurnal sleep patterns ( [Hoffmann et al., 2012][5]). Advances in applying wireless technology for recording neural activity during natural, unrestrained behaviors ( [Walker et al., 2021][6]) position the marmoset as an excellent model for studying sleep-related neural activity associated with learning. Here, we identify putative SWS epochs based on the spatially correlated activity of local field potentials (LFPs) recorded from a multielectrode planar array implanted in the sensorimotor cortex of two marmosets (one female and one male). The averag...

ArfGAP, with dual PH domain-containing protein 1/Centaurin-α1 (ADAP1/CentA1), is a brain-enriched and highly conserved Arf6 GTPase-activating and Ras-anchoring protein. CentA1 is involved in dendritic outgrowth and arborization, synaptogenesis, and axonal polarization by regulating the actin cytoskeleton dynamics. CentA1 upregulation and association with amyloid plaques in the human Alzheimer's disease (AD) brain suggest the role of this protein in AD progression. To understand the role of CentA1 in neurodegeneration, we crossbred CentA1 knock-out (KO) mice with the J20 mouse model of AD. We evaluated AD-associated behavioral and neuropathological hallmarks and gene expression profiles in J20 and J20 crossed with CentA1 KO (J20xKO) male mice to determine the impact of eliminating CentA1 expression on AD-related phenotypes. Spatial memory assessed by the Morris water maze test showed significant impairment in J20 mice, which was rescued in J20xKO mice. Moreover, neuropathological hallmarks of AD, such as am...

Structural changes in dendritic spines underlie long-term potentiation (LTP). While CaMKII has been considered as the primary driver of these changes, we show that transient, localized activation of Rac1 alone is sufficient to induce structural LTP in hippocampal slices prepared from rat pups of either sex. Using photoactivatable Rac1 (PA-Rac1), we demonstrated that Rac1 activation triggers spine enlargement and actin polymerization. This PA-Rac1-induced plasticity was blocked by Rac1 and Pak1 inhibitors but not by a CaMKII inhibitor. Our results identify Rac1 as an upstream of persistent signaling that stabilizes actin-based spine structural changes critical for synaptic memory encoding.

Attachment theory offers an important clinical framework for understanding and treating negative effects of early life adversity. Attachment styles emerge during critical periods of development in response to caregivers' ability to consistently meet their offspring’s needs. Attachment styles are classified as secure or insecure (anxious, avoidant, or disorganized), with rates of insecure attachment rising in high-risk populations and correlating with a plethora of negative health outcomes throughout life. Despite its importance, little is known about the neural basis of attachment. Work in rats has demonstrated that limited bedding and nesting (LB) impairs maternal care and produces abnormal maternal attachment linked to increased pup corticosterone. However, the effects of LB on attachment-like behavior have not been investigated in mice where additional genetic and molecular tools are available. Furthermore, no group has utilized home-cage monitoring to link abnormal maternal care with deficits in attach...

In natural, free-viewing settings, visual perception is driven by a series of saccades and fixations. Perceptual mechanisms are typically studied through averaged fixation-related potentials generated from simultaneous eye-tracking and EEG recordings. Lambda responses following fixation onsets signal the arrival of new visual input to the primary visual cortex. In our study, we investigate the use and preprocessing parameter dependence of independent component analysis (ICA) in separating the lambda response from other neural sources. In our experiment, 10 subjects (2 males and 8 females) viewed 80 art paintings in natural, free-viewing settings, during which EEG data were recorded. Our results show that unique lambda response components can be detected reliably and individual lambda waves can be extracted in a single-trial manner, without signal averaging. ICA decomposition is most sensitive to high-pass filtering producing best results with a minimum 1 Hz filtering. We also propose a method that automati...