The scientific landscape in the United States is experiencing a significant shift. Recent developments have created new challenges for US researchers, US institutions, and scientific societies worldwide that warrant our collective attention and thoughtful response. These changes present an opportunity to reaffirm the fundamental importance of scientific exchange. Recent policy changes have significantly altered funding for biomedical research in the United States. The National Institutes of Health (NIH) has announced substantial reductions in funding and has canceled study sections. Although the story is still unravelling, the decision to limit the overheads to 15% may threaten the very existence of some laboratories with obvious disastrous human consequences. This also includes the closure of NIH-core funded facilities and the firing of scientific personnel. The current climate has changed the way international researchers consider future travel to the United …

In the article “Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation,” by Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa, and Ana João Rodrigues, …

T-Type calcium channels shape neuronal excitability driving burst firing, plasticity, and neuronal oscillations that influence circuit activity. The three biophysically distinct T-type channel subtypes (Cav3.1, Cav3.2, Cav3.3) are differentially expressed in the brain, contributing to divergent physiological processes. Cav3.2 channels are highly expressed in the dentate gyrus (DG) of the hippocampus, and mice lacking Cav3.2 [knock-out (KO)] exhibit impairments in hippocampal dependent learning and memory tasks, as well as attenuated development of pilocarpine induced epilepsy. Owing to neurogenesis, granule cells (GCs) are continuously added to the DG, generating a heterogeneous population of maturational stages with distinct excitability. While initial studies identified the role of Cav3.2 in mature GC burst firing, its functional relevance in the intrinsic excitability of different GC subpopulations has not yet been examined. In this study, we used juvenile Cav3.2 KO mice to examine the contributions of ...

Auditory masking—the interference of the encoding and processing of an acoustic stimulus imposed by one or more competing stimuli—is nearly omnipresent in daily life and presents a critical barrier to many listeners, including people with hearing loss, users of hearing aids and cochlear implants, and people with auditory processing disorders. The perceptual aspects of masking have been actively studied for several decades, and particular emphasis has been placed on masking of speech by other speech sounds. The neural effects of such masking, especially at the subcortical level, have been much less studied, in large part due to the technical limitations of making such measurements. Recent work has allowed estimation of the auditory brainstem response (ABR), whose characteristic waves are linked to specific subcortical areas, to naturalistic speech. In this study, we used those techniques to measure the encoding of speech stimuli that were masked by one or more simultaneous other speech stimuli. We presented...

Response preparation is accomplished by gradual accumulation in neural activity until a threshold is reached. In humans, such a preparatory signal, referred to as the lateralized readiness potential (LRP), can be observed in the EEG over sensorimotor cortical areas before execution of a voluntary movement. Although well described for manual movements, less is known about preparatory EEG potentials for saccadic eye movements in humans and nonhuman primates. Hence, we describe a LRP over the frontolateral cortex in macaque monkeys. Homologous to humans, we observed lateralized electrical potentials ramping before the execution of both rewarded and nonrewarded contralateral saccades. This potential parallels the neural spiking of saccadic movement neurons in the frontal eye field (FEF), suggesting that it may offer a noninvasive correlate of intracortical spiking activity. However, unlike neural spiking in the FEF, polarization in frontolateral channels did not distinguish between saccade generation and inhib...

Humans can adapt their movements in response to expected and unexpected perturbations. The speed and accuracy of these movement corrections may depend on the type of sensory information driving the perception of these perturbations. While previous research has indicated that corrections based on somatosensory information, comprised of proprioceptive and tactile inputs, are faster than corrections based on visual information, other studies have found comparable correction speeds in response to visual and tactile inputs. The purpose of this study was to systematically investigate the latencies (how fast) and magnitudes (how large) of movement corrections in response to perturbations of external visual targets, as well as somatosensory (proprioceptive and tactile) and tactile targets on the non-reaching limb. Participants performed reaching movements to a light-emitting diode (i.e., visual target), the felt position of a brush touching the index finger of the non-reaching hand (i.e., a tactile target), and th...

A decline in cognitive abilities is associated with the aging process, affecting nearly 33% of US adults over the age of 70, and is a risk factor for the development of dementia and Alzheimer's disease. Several studies have reported age-related alterations in the transcriptome in the hippocampus, a major site of memory storage that is among the first regions impacted with age, dementia, and Alzheimer's disease. However, much remains unknown about why these transcriptional changes exist in the aged hippocampus and how this impacts memory late in life. Here, we show that monoubiquitination of histone H2B (H2Bubi), an epigenetic mechanism recently reported to be major regulator of the epigenome and transcriptome during memory formation in the young adult brain, decreases with age in the hippocampus of male rats. In vivo CRISPR-dCas9–mediated upregulation of Rnf20 , the only ubiquitin E3 ligase for H2B, in the hippocampus significantly improved memory retention in aged rats. Remarkably, RNA-seq analysis reveal...

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by specific morphological and electrophysiological properties. First, in ∼90% of the cases, their axon arises from an axon-bearing dendrite (ABD) at highly variable distances from the soma. Second, they display a highly regular pattern of spontaneous activity (aka pacemaking) and a broad action potential (AP) that faithfully back-propagates through the entire dendritic arbor. In previous studies ( [Moubarak et al., 2019][1]; [Moubarak et al., 2022][2]), we demonstrated that the presence of a high density of sodium current in the ABD and the complexity of this dendrite played a critical role in the robustness of pacemaking and setting the half-width of the AP. In the current study, we investigated the postnatal development of both morphology and AP shape in SNc DA neurons in order to determine when and how the mature electrophysiological phenotype of these neurons was achieved. To do so, we performed electrophysiological record...

Human motor skill acquisition is improved by performance feedback, and coupling such feedback with extrinsic reward (such as money) can enhance skill learning. However, the neurophysiology underlying such behavioral effect is unclear. To bridge this gap, we assessed the effects of reward on multiple forms of motor plasticity during skill learning. Sixty-five healthy participants divided into three groups performed a pinch-grip skill task with sensory feedback only, sensory and reinforcement feedback, or both feedback coupled with an extrinsic monetary reward during skill training. To probe motor plasticity, we applied transcranial magnetic stimulation at rest, on the left primary motor cortex before, at an early-training time point, and after training in the three groups and measured motor-evoked potentials from task-relevant muscle of the right arm. This allowed us to evaluate the amplitude and variability of corticospinal output, GABAergic short-intracortical inhibition, and use-dependent plasticity befo...

Perceptual decision-making describes the process of selecting an appropriate action based on the sensory information present in the immediate environment and is hence an omnipresent factor in the life of animals. In preclinical research, a widespread approach to study the neuronal correlates of perceptual decision-making is to record (and manipulate) neuronal activity in head-fixed mice performing behavioral tasks. In contrast to the technologies used to record/manipulate neuronal activity, standardization of the behavioral training of mice is generally neglected, a circumstance that is particularly true for behavioral tasks involving auditory stimuli. Here, we present the DMC-Behavior Platform, an open-source, cost-efficient framework for training head-fixed mice in perceptual decision-making tasks involving auditory stimuli. Combining the DMC-Behavior Platform with strategies to record and manipulate neuronal activity offers many opportunities to test hypotheses on the neuronal underpinnings of cognitive...