Each stage of a scientist's career is filled with unique challenges that seem like roadblocks to becoming an advocate. Graduate school is no exception, but early career scientists should be advocating for science, as what this year’s budget provides can alter our career trajectories. As a graduate student, I first thought there wasn’t much I could do, and that advocacy could only be effective if it was intense and all consuming. Even if I figured out what to do, it seemed like it would be too much. I soon found this assumption to be false.

Scientific progress often hinges on the courage to question conventional models and embrace exploratory research. This commentary examines the importance of curiosity-driven science by drawing on historical and contemporary examples, from Darwin's unconventional research methodologies to modern neuroscience investigations that challenge the constraints of traditional laboratory environments. An over-reliance on predictable, controlled conditions—particularly in select rodent models—has potentially limited the translational impact of neuroscience. By exploring novel research paradigms, including raccoon neural investigations and rodent-driven vehicles (ROVs), the value of expanding research models to incorporate diverse species and environments is examined. As neuroscience advances, the field must move beyond the metaphorical lamp post, venturing into uncharted territory to fully capture the complexity of neurobiological variables. By fostering a culture of discovery over predictability—supported by innovat...

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...

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 ...

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...

Behavioral and neuroscientific studies have shown that watching a speaker's lip movements aids speech comprehension. Intriguingly, even when videos of speakers are presented silently, various cortical regions track auditory features, such as the envelope. Recently, we demonstrated that eye movements track low-level acoustic information when attentively listening to speech. In this study, we investigated whether ocular speech tracking occurs during visual speech and how it influences cortical silent speech tracking. Furthermore, we compared data from hearing individuals, congenitally deaf individuals, and those who became deaf or hard of hearing (DHH) later in life to assess how audiovisual listening experience and auditory deprivation (early vs late onset) affect neural and ocular speech tracking during silent lip-reading. Using magnetoencephalography (MEG), we examined ocular and neural speech tracking of 75 participants observing silent videos of a speaker played forward and backward. Our main finding is...

Synchronous activity of neuronal networks is found in many brain areas and correlates with cognition and behavior. Gamma synchrony is particularly strong in the dentate gyrus, which is thought to process contextual information in the hippocampus. Several network mechanisms for synchrony generation have been proposed and studied computationally. One such mechanism relies solely on recurrent inhibitory interneuron connectivity, but it requires a large enough number of synapses. Here, we incorporate previously published connectivity data of the dentate gyrus from mice of either sex into a biophysical computational model to test its ability to generate synchronous activity. We find that recurrent interneuron connectivity is insufficient to induce synchronous activity. This applies to an interneuron ring network and the broader dentate gyrus circuitry. Despite asynchronous input, recurrent interneuron connectivity can have small synchronizing effects but can also desynchronize the network for some types of syna...

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...

Investigation of neural processes underlying motor control requires behavioral readouts that capture the richness of actions, including both categorical (choice-based) information and motor execution (kinematics). We present an open-source platform for behavioral training of head-fixed mice that combines a stationary or retractable forelimb-based joystick, sound-presentation system, capacitive lick sensor, and water reward dispenser. The setup allows for the creation of multiple behavioral paradigms, two of which are highlighted here: a two-alternative forced-choice auditory-motor discrimination paradigm and a two-armed bandit value-based decision-making task. In the auditory-motor paradigm, mice learn to report high- or low-frequency tones by pushing or pulling the joystick. In the value-based paradigm, mice learn to push or pull the joystick based on the history of rewarded trials. In addition to reporting categorical choices, this setup provides a rich dataset of motor parameters that reflect components...