Lumbar erector spinae (LES) contribute to spine postural and voluntary control. Transcranial magnetic stimulation (TMS) preferentially depolarizes different neural circuits depending on the direction of electrical currents evoked in the brain. Posteroanterior current (PA-TMS) and anteroposterior (AP-TMS) current would, respectively, depolarize neurons in the primary motor cortex (M1) and the premotor cortex. These regions may contribute differently to LES control. This study examined whether responses evoked by PA- and AP-TMS are different during the preparation and execution of LES voluntary and postural tasks. Participants performed a reaction time task. A Warning signal indicated to prepare to flex shoulders (postural; n  = 15) or to tilt the pelvis (voluntary; n  = 13) at the Go signal. Single- and paired-pulse TMS (short-interval intracortical inhibition—SICI) were applied using PA- and AP-TMS before the Warning signal (baseline), between the Warning and Go signals (preparation), or 30 ms before the L...

For comprehensive anatomical analysis of a mouse brain, accurate and efficient registration of the experimental brain samples to a reference atlas is necessary. Here, we introduce Bell Jar, a semiautomated solution that can align and annotate tissue sections with anatomical structures from a reference atlas as well as detect fluorescent signals with cellular resolution (e.g., cell bodies or nuclei). Bell Jar utilizes Mattes mutual information-directed B-spline transformations to achieve precise alignments, even with damaged sample tissues. While user input remains a requirement for fine-tuning section matches, the platform streamlines the process, aiding rapid analyses in high-throughput neuroanatomy studies. As a standalone desktop application with a user-friendly interface, Bell Jar’s performance, which surpasses traditional manual and existing automated methods, can improve the reproducibility and throughput of histological analyses.

High-frequency stimulation (HFS)-induced long–term potentiation (LTP) is generally regarded as a homosynaptic Hebbian-type LTP, where synaptic changes are thought to occur at the synapses that project from the stimulation site and terminate onto the neurons at the recording site. In this study, we first investigated HFS-induced LTP on urethane-anesthetized rats and found that cortical HFS enhances neural responses at the recording site through the strengthening of local connectivity with nearby neurons at the stimulation site rather than through synaptic strengthening at the recording site. This enhanced local connectivity at the stimulation site leads to increased output propagation, resulting in signal potentiation at the recording site. Additionally, we discovered that HFS can also nonspecifically strengthen distant afferent synapses at the HFS site, thereby expanding its impact beyond local neural connections. This form of plasticity exhibits a neo-Hebbian characteristic as it exclusively manifests in ...

Fear generalization is a hallmark of anxiety disorders. Experimentally, fear generalization can be difficult to dissociate from its counterpart, fear discrimination. Here, we use minimal threat learning procedures to reveal such a dissociation. We show that in Long–Evans rats, an auditory threat cue predicting footshock on 10% of trials produces a discriminated fear response that does not generalize to a neutral auditory cue. In contrast, even slightly higher footshock probabilities (30 and 20%) produce fear generalization. AAV-mediated, caspase-3 deletion of ventral pallidum neurons abolishes fear generalization and reduces threat cue responding during extinction. The ventral pallidum's contribution to fear generalization and extinction threat responding does not depend on inputs from the nucleus accumbens. The results demonstrate a minimal threat learning approach to dissociate fear discrimination from fear generalization and a novel role for the ventral pallidum in generalizing and expressing fear.

Hydroxychloroquine (HCQ), a well-known antimalarial and anti-inflammatory drug, has demonstrated potential neuroprotective effects in ischemic stroke by inhibiting pyroptosis, a programmed cell death associated with inflammation. This study investigates the impact of HCQ on ischemic stroke pathology using both in vivo and in vitro models. In vivo, C57BL/6 mice subjected to middle cerebral artery occlusion (MCAO) were treated with HCQ. Neurological deficits, infarct volume, and the expression of pyroptosis markers were evaluated. The results demonstrated that HCQ significantly improved motor function and reduced infarct volume in the MCAO mouse model. In vitro, BV2 microglial cells exposed to lipopolysaccharide (LPS) and oxygen–glucose deprivation (OGD) were treated with HCQ. Western blot and immunofluorescence analyses revealed that HCQ effectively suppressed the expression of pyroptosis markers GSDMD and NLRP3 in both in vivo and in vitro models. These findings suggest that HCQ mitigates ischemic stroke d...

The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked is a population of immune cells that also resides within the gland but whose distribution and function are not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early postnatal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-IR neuronal varicosities and juxtaposed to CD31-IR blood vessels. Using Lyz2cre-GCaMP6f mice to quantify calcium signaling in macrophages revealed these cells respond directly and indirectly to a wide variety of neuromodulators, including pre- and postganglionic transmitters and systemic hormones. Purinergic agonists, histamine, acetylcholine, and bradykinin rapidly and re...

Extended performance of cognitively demanding tasks induces cognitive fatigue manifested with an overall deterioration of behavioral performance. In particular, long practice with tasks requiring impulse control is typically followed by a decrease in self-control efficiency, leading to performance instability. Here, we show that this is due to changes in activation modalities of key task-related areas occurring if these areas previously underwent intensive use. We investigated in 25 healthy adults the effects of extended practice with high cognitive demand (HCD) tasks on a Go-No Go task and the underlying electroencephalographic (EEG) activity. We compared these effects with those induced by practice with similar, but low cognitive demand (LCD) tasks. HCD tasks were followed by an increase in response inhibition failures. These were correlated with the appearance of a distinct neural signature on fast response trials, characterized by lower levels of beta ([13–30] Hz) EEG activity in the prestimulus period...

Why does groundbreaking progress in our understanding of the brain seem scarce (at least to me)? The prevailing system of research funding and publication, deeply rooted in peer review and contingent upon preliminary data, tends to favor safe, conventional ideas, thereby impeding major breakthroughs. The prerequisite of preliminary data for hypothesis validation transforms grant-seeking into a cycle that prioritizes data accumulation over pioneering ideas, fostering publications that align with pre-established notions endorsed by reviewers. Are we, the scientists, becoming akin to the subjects of our experiments? Consider this: in behavioral studies, rodents are often deprived of food and water to motivate their learning of a task. Since a successful task is rewarded, animals quickly learn the task and become very efficient at it after some time. Now, envision neuroscientists in a similar plight, navigating the pursuit of funding and recognition in high-profile journals. This predicament is faced by many (...

Transgenic mice provide unprecedented access to manipulate and visualize neural circuits; however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST- Cdh23Ahl + mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high-frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, Ahl+ C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4–64 kHz, 30–90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for generating complex geno...

Prenatal exposure to high-energy diets (HED) increases the susceptibility to behavioral alterations in the male offspring. We addressed whether prenatal HED primes the transgenerational inheritance of structural brain changes impacting anxiety/depression-like behavior in the offspring. For this, we used female Wistar rats exposed to a HED [cafeteria (CAF) diet, n  = 6] or chow [control (CON) n  = 6] during development. Anxiety and depression-like behavior were evaluated in filial 1 (F1), filial 2 (F2), and filial 3 (F3) male offspring using the open field (OFT), elevated plus maze, novelty suppressed feeding (NSFT), tail suspension (TST), and forced swimming tests. Structural brain changes were identified by deformation-based morphometry (DBM) and diffusion tensor imaging using ex vivo MRI. We found that the F1, F2, and F3 offspring exposed to CAF diet displayed higher anxious scores including longer feeding latency during the NSFT, and in the closed arms, only F1 offspring showed longer stay on edges duri...