Oscillatory activity in the human brain is dominated by posterior alpha oscillations (8–14 Hz), which have been shown to be functionally relevant in a wide variety of cognitive tasks. Although posterior alpha oscillations are commonly considered a single oscillator anchored at an individual alpha frequency (∼10 Hz), previous work suggests that individual alpha frequency reflects a spatial mixture of different brain rhythms. In this study, we assess whether independent component analysis (ICA) can disentangle functionally distinct posterior alpha rhythms in the context of visual short-term memory retention. Magnetoencephalography (MEG) was recorded in 33 subjects while performing a visual working memory task. Group analysis at sensor level suggested the existence of a single posterior alpha oscillator that increases in power and decreases in frequency during memory retention. Conversely, single-subject analysis of independent components revealed the existence of two dissociable alpha rhythms: one that incre...

Given its inputs from auditory structures and neuromodulatory systems, the posterior tail of the striatum is ideally positioned to influence behavioral responses to acoustic stimuli according to context and previous rewards. Results from previous studies indicate that neurons in this striatal region display selective responses to sounds. However, it is not clear whether different striatal cell classes code for distinct features of sounds or how different striatal output pathways may use acoustic information to guide behavior. Here we compared the sound-evoked responses of posterior striatal neurons that form the striatal direct pathway (and express the dopamine receptor D1) to the responses of neighboring neurons in naive mice. We achieved this via optogenetic photo-identification of D1-expressing neurons during extracellular electrophysiological recordings in awake head-fixed mice of both sexes. We found that the frequency tuning of sound-responsive direct-pathway striatal neurons is comparable with that ...

Experiments employing chronic monitoring of neurophysiological signals and video are commonly used in studies of epilepsy to characterize behavioral correlates of seizures. Our objective was to design a low-cost platform that enables chronic monitoring of several animals simultaneously, synchronizes bilateral local field potential (LFP) and video streams in real time, and parses recorded data into manageable file sizes. We present a hardware solution leveraging Intan and Open Ephys acquisition systems and a software solution implemented in Bonsai. The platform was tested in 48-h continuous recordings simultaneously from multiple mice (male and female) with chronic epilepsy. To enable seizure detection and scoring, we developed a graphical user interface (GUI) that reads the data produced by our workflow and allows a user with no coding expertise to analyze events. Our Bonsai workflow was designed to maximize flexibility for a wide variety of experimental applications, and our use of the Open Ephys acquisit...

Functional magnetic resonance imaging (fMRI) combined with population receptive field (pRF) mapping allows for associating positions on the visual cortex to areas on the visual field. Apart from applications in healthy subjects, this method can also be used to examine dysfunctions in patients suffering from partial visual field losses. While such objective measurement of visual deficits (scotoma) is of great importance for, e.g., longitudinal studies addressing treatment effects, it requires a thorough assessment of accuracy and reproducibility of the results obtained. In this study, we quantified the reproducibility of pRF mapping results within and across sessions in case of central visual field loss in a group of 15 human subjects. We simulated scotoma by masking a central area of 2° radius from stimulation to establish ground-truth conditions. This study was performed on a 7T ultra-high field MRI scanner for increased sensitivity. We found excellent intrasession and intersession reproducibility for the...

Opsin-3 ( Opn3 , encephalopsin) was the first nonvisual opsin gene discovered in mammals. Since then, several Opn3 functions have been described, and in two cases (adipose tissue, smooth muscle) light sensing activity is implicated. In addition to peripheral tissues, Opn3 is robustly expressed within the central nervous system, for which it derives its name. Despite this expression, no studies have investigated developmental or adult CNS consequences of Opn3 loss-of-function. Here, the behavioral consequences of mice deficient in Opn3 were investigated. Opn3 -deficient mice perform comparably to wild-type mice in measures of motor coordination, socialization, anxiety-like behavior, and various aspects of learning and memory. However, Opn3 -deficient mice have an attenuated acoustic startle reflex (ASR) relative to littermates. This deficit is not because of changes in hearing sensitivity, although Opn3 was shown to be expressed in auditory and vestibular structures, including cochlear outer hair cells. Int...

Limited reproducibility and validity are major sources of concern in biology and other fields of science. Their origins have been extensively described and include material variability, incomplete materials and methods report, results selection, defective experimental design, lack of power, inappropriate statistics, overinterpretation, and reluctance to publish negative results. Promoting complete and accurate communication of positive and negative results is a major objective. Multiple steps in this direction are taken, but they are not sufficient and the general construction of articles has not been questioned. I propose here a simple change with a potentially strong positive impact. First, when they complete a substantial coherent set of experiments, scientists deposit their positive or negative results in a database [“deposited results,” (DRs)], including detailed materials, methods, raw data, analysis, and processed results. The DRs are technically reviewed and validated as “validated DRs” (vDRs) or r...

This study assesses the involvement in human motor learning, of the ventrolateral prefrontal cortex (BA 9/46v), a somatic region in the middle frontal gyrus. The potential involvement of this cortical area in motor learning is suggested by studies in nonhuman primates which have found anatomic connections between this area and sensorimotor regions in frontal and parietal cortex, and also with basal ganglia output zones. It is likewise suggested by electrophysiological studies which have shown that activity in this region is implicated in somatic sensory memory and is also influenced by reward. We directly tested the hypothesis that area 9/46v is involved in reinforcement-based motor learning in humans. Participants performed reaching movements to a hidden target and received positive feedback when successful. Before the learning task, we applied continuous theta burst stimulation (cTBS) to disrupt activity in 9/46v in the left or right hemisphere. A control group received sham cTBS. The data showed that cT...

A strong bidirectional link between metabolic and psychiatric disorders exists; yet the molecular basis underlying this interaction remains unresolved. Here we explored the role of the brown fat issue (BAT) as modulatory interface, focusing on the involvement of uncoupling protein 1 (UCP-1), a key metabolic regulator highly expressed in BAT, in the control of emotional behavior. Male and female constitutive UCP-1 knockout (KO) mice were used to investigate the consequences of UCP-1 deficiency on anxiety-related and depression-related behaviors under mild thermogenic (23°C) and thermoneutral (29°C) conditions. UCP-1 KO mice displayed a selective enhancement of anxiety-related behavior exclusively under thermogenic conditions, but not at thermoneutrality. Neural and endocrine stress mediators were not affected in UCP-1 KO mice, which showed an activation of the integrated stress response alongside enhanced Fibroblast-growth factor-21 (FGF-21) levels. However, viral-mediated overexpression of FGF-21 did not...

Low-frequency (<200 Hz), subperception spinal cord stimulation (SCS) is a novel modality demonstrating therapeutic efficacy for treating chronic neuropathic pain. When stimulation parameters were carefully titrated, patients experienced rapid onset (seconds–minutes) pain relief without paresthesia, but the mechanisms of action are unknown. Using an integrated computational model and in vivo measurements in urethane-anesthetized rats, we quantified how stimulation parameters (placement, pulse width, frequency, and amplitude) influenced dorsal column (DC) axon activation and neural responses in the dorsal horn (DH). Both modeled and recorded DC axons responded with irregular spiking patterns in response to low-amplitude SCS. Maximum inhibition of DH neurons occurred at ∼80% of the predicted sensory threshold in both modeled and recorded neurons, and responses were strongly dependent on spatially targeting of stimulation, i.e., the complement of DC axons activated, and on stimulation parameters. Intrathecal a...

It has been suggested that the dorsomedial striatum (DMS) is engaged in the early stages of motor learning for goal-directed actions, whereas at later stages, control is transferred to the dorsolateral striatum (DLS), a process that enables learned motor actions to become a skill or habit. It is not known whether these striatal regions are simultaneously active while the expertise is acquired. To address this question, we developed a mouse “Treadmill Training Task” that tracks changes in mouse locomotor coordination during running practice and simultaneously provides a means to measure local neuronal activity using photometry. To measure change in motor coordination over treadmill practice sessions, we used DeepLabCut (DLC) and custom-built code to analyze body position and paw movements. By evaluating improvements in motor coordination during training with simultaneous neuronal calcium activity in the striatum, we found that DMS direct pathway neurons exhibited decreased activity as the mouse gained profi...