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...

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...

The re-emergence of task-related activation patterns during awake rest has been reported to play a role in memory consolidation and perceptual learning. This study aimed to test whether such reactivation occurs in the primary sensorimotor cortex following a visuomotor task. During functional magnetic resonance imaging (fMRI) scanning, 42 healthy participants (13 women and 29 men) learned visuomotor tracking, while a rotational perturbation was introduced between the cursor position and joystick angle. This visuomotor task block was interleaved with a control block, during which participants passively viewed a replay of their previously performed cursor movements. Half of the participants used their right hand, whereas the other half used their left hand to control the joystick. Resting-state scans were acquired before and after the visuomotor task sessions. A multivariate pattern classifier was trained to classify task and control blocks and was then tested on resting-state scans collected before and after...

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...

The importance of animal models to an understanding of the development and plasticity of visual functions was evident from the outset of the long experimental collaboration of David Hubel and Torsten Wiesel in the early 1960s. Their initial work on kittens had massive impact in part because of the recognition that kittens share with primates substantial similarities of visual system organization and plasticity (e.g., eye-specific lamination of the thalamus and columnar organization of the visual cortex), as well as comparable visual abilities (including stereoscopic vision). In addition the plasticity demonstrated in response to early periods of selected visual exposure provided a glimpse into the origins of amblyopia. Five decades ago my laboratory developed a method for the fast measurement of visual thresholds in kittens in order to capture the consequences for spatial vision of the rapid physiological changes that occurred in the visual cortex during both typical development and those that follow vario...

Mouse lines with tetracycline-controlled gene expression in specific neuronal populations provide valuable tools for studying their development, function, connectivity, and pathology in vivo. Our initial goal was to generate a mouse model that could express amyotrophic lateral sclerosis-associated genes specifically in spinal cord motor neurons under the control of the HB9 promoter. However, HB9-tTA mice unexpectedly direct target gene expression in a small subset of dorsal horn neurons. These mice represent a new tool for scientists who are interested in studying these spinal cord neurons.

Early and accurate diagnosis of Alzheimer's disease (AD) will be key for effective personalized treatment plans ( [Cummings, 2023][1]). Significant difficulties in auditory processing have been frequently reported in many patients with mild cognitive impairment, the prodromal form of AD ( [Tarawneh et al., 2022][2]), making it an outstanding candidate as AD diagnostic biomarker. However, the efficiency of diagnosis with this parameter has not been explored. Here we show that when male mice with amyloidosis begin to show memory decline, changes in the auditory brainstem response (ABR) to clicks enable the reliable diagnosis of disease using a machine learning algorithm. Interpretation of the machine learning diagnosis revealed that the upper levels of the auditory pathway, including the inferior colliculus, were the probable sources of the defects. Histological analyses show that in these locations, neuroinflammation and plaque deposition temporally correlate with behavioral changes consistent with memory l...

Individuals with normal hearing exhibit considerable variability in their capacity to understand speech in noisy environments. Previous research suggests the cause of this variance may be due to individual differences in cognition and auditory perception. To investigate the impact of cognitive and perceptual differences on speech comprehension, 25 adult human participants with normal hearing completed numerous cognitive and psychoacoustic tasks including the Flanker, Stroop, Trail Making, reading span, and temporal fine structure tests. They also completed a continuous multitalker spatial attention task while neural activity was recorded using electroencephalography. The auditory cortical N1 response was extracted as a measure of neural speech encoding during continuous speech listening using an engineered “chirped-speech” (Cheech) stimulus. We compared N1 component morphologies of target and masker speech stimuli to assess neural correlates of attentional gains while listening to concurrently played short...

What the basal ganglia do is an oft-asked question; answers range from the selection of actions to the specification of movement to the estimation of time. Here, I argue that how the basal ganglia do what they do is a less-asked but equally important question. I show that the output regions of the basal ganglia create a stringent computational bottleneck, both structurally, because they have far fewer neurons than do their target regions, and dynamically, because of their tonic, inhibitory output. My proposed solution to this bottleneck is that the activity of an output neuron is setting the weight of a basis function, a function defined by that neuron’s synaptic contacts. I illustrate how this may work in practice, allowing basal ganglia output to shift cortical dynamics and control eye movements via the superior colliculus. This solution can account for troubling issues in our understanding of the basal ganglia: why we see output neurons increasing their activity during behavior, rather than only decreas...