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...

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...

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...

Attention-deficit/hyperactivity disorder (ADHD) adversely affects the learning, social interaction, and daily living of affected children. Atomoxetine (ATX) hydrochloride (HCI) has been widely used in clinical practice. Electroencephalogram (EEG) biofeedback, as a nonpharmacological treatment approach, has also demonstrated potential in improving symptoms in children with ADHD. We aimed to investigate the clinical efficacy of combining ATX HCI with EEG biofeedback in the treatment of ADHD in children. We hypothesized that this combined therapy would be more effective in alleviating symptoms in children with ADHD. Ninety children with ADHD were randomly separated into the control group (receiving ATX HCI treatment for 12 weeks) and study group (receiving ATX HCI treatment for 12 weeks combined with 60 sessions of EEG biofeedback treatment; n  = 45). Swanson, Nolan, and Pelham-IV (SNAP-IV) rating scale scores, integrated visual and auditory continuous performance test results, Conners parent symptom question...

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...