Birds are exceptionally adept at controlling their body position. For example, they can coordinate rapid movements of their body while stabilizing their head. Intriguingly, this ability may rely in part on a mechanosensory organ in the avian lower spinal cord called the lumbosacral organ (LSO). However, molecular mechanotransduction mechanisms have not been identified in the avian spinal cord. Here, we report the presence of glycinergic neurons in the LSO that exhibit immunoreactivity for myosin7a and espin, molecules essential for function and maintenance of hair cells in the inner ear. Specifically, we find glycinergic cell bodies near the central canal and processes that extend laterally to the accessory lobes and spinal ligaments. These LSO neurons are reminiscent of glycinergic neurons in a recently-described lateral spinal proprioceptive organ in zebrafish that detects spinal bending. The avian LSO, however, is located inside a series of fused vertebrae called the synsacrum, which constrains spinal b...

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...

The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Recent experiments showed that recurring cholinergic activation of α7 nACh receptors expressed in oriens-lacunosum-moleculare (OLMα2) interneurons can directly induce LTP in Schaffer collateral (SC)–CA1 synapses. Here, we pair in vitro studies with biophysically based modeling to uncover the underlying mechanisms. According to our model, α7 nAChR activation increases OLM GABAergic activity. This results in the inhibition of the fast-spiking interneurons that provide feedforward inhibition onto CA1 pyramidal neurons. This disinhibition, paired with tightly timed SC stimulation, can induce potentiation at the excitatory synapses of CA1 pyramidal neurons. Our work details the role of cholinergic modulation in disinhibition-induced hippocampal plasticity. It relates the timing of ch...

fMRI studies that investigate somatotopic tactile representations in the human cortex typically use either block or phase-encoded stimulation designs. Event-related (ER) designs allow for more flexible and unpredictable stimulation sequences than the other methods, but they are less efficient. Here, we compared an efficiency-optimized fast ER design (2.8-s average intertrial interval; ITI) to a conventional slow ER design (8-s average ITI) for mapping voxelwise fingertip tactile tuning properties in the sensorimotor cortex of six participants at 7 Tesla. The fast ER design yielded more reliable responses compared with the slow ER design, but with otherwise similar tuning properties. Concatenating the fast and slow ER data, we demonstrate in each individual brain the existence of two separate somatotopically-organized tactile representations of the fingertips, one in the primary somatosensory cortex (S1) on the postcentral gyrus, and the other shared across the motor and premotor cortices on the precentral ...

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...

The 1/ f spectral slope of the electroencephalogram (EEG) estimated in the γ frequency range has been proposed as an arousal marker that differentiates wake, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Here, we sought to replicate and extend these findings in a large sample, providing a comprehensive characterization of how slope changes with age, sex, and its test-retest reliability as well as potential confounds that could affect the slope estimation. We used 10,255 whole-night polysomnograms (PSGs) from the National Sleep Research Resource (NSRR). All preprocessing steps were performed using an open-source Luna package and the spectral slope was estimated by fitting log-log linear regression models on the absolute power from 30 to 45 Hz separately for wake, NREM, and REM stages. We confirmed that the mean spectral slope grows steeper going from wake to NREM to REM sleep. We found that the choice of mastoid referencing scheme modulated the extent to which electromyogenic, or e...

What we see is intimately linked to how we actively and systematically explore the world through eye movements. However, it is unknown to what degree visual experience during early development is necessary for such systematic visual exploration to emerge. The present study investigated visual exploration behavior in 10 human participants whose sight had been restored only in childhood or adulthood, after a period of congenital blindness because of dense bilateral congenital cataracts. Participants freely explored real-world images while their eye movements were recorded. Despite severe residual visual impairments and gaze instability (nystagmus), visual exploration patterns were preserved in individuals with reversed congenital cataract. Modeling analyses indicated that, similar to healthy control subjects, visual exploration in individuals with reversed congenital cataract was based on the low-level (luminance contrast) and high-level (object components) visual content of the images. Moreover, participant...

Fragile X syndrome (FXS) is a leading monogenic cause of intellectual disability and autism spectrum disorders, spurring decades of intense research and a multitude of mouse models. So far, these models do not recapitulate the genetic underpinning of classical FXS—CGG repeat-induced methylation of the Fmr1 locus—and their findings have failed to translate into the clinic. We sought to answer whether this disparity was because of low repeat length and generated a novel mouse line with 341 repeats, Fmr1hs341 , which is the largest allele in mice reported to date. This repeat length is significantly longer than the 200 repeats generally required for methylation of the repeat tract and promoter region in FXS patients, which leads to silencing of the FMR1 gene. Bisulfite sequencing fails to detect the robust methylation expected of FXS in Fmr1hs341 mice. Quantitative real-time PCR and Western blotting results also do not resemble FXS and instead produce a biochemical profile consistent with the fragile X-associ...

The development of validated algorithms for automated handling of artifacts is essential for reliable and fast processing of EEG signals. Recently, there have been methodological advances in designing machine-learning algorithms to improve artifact detection of trained professionals who usually meticulously inspect and manually annotate EEG signals. However, validation of these methods is hindered by the lack of a gold standard as data are mostly private and data annotation is time consuming and error prone. In the effort to circumvent these issues, we propose an iterative learning model to speed up and reduce errors of manual annotation of EEG. We use a convolutional neural network (CNN) to train on expert-annotated eyes-open and eyes-closed resting-state EEG data from typically developing children ( n = 30) and children with neurodevelopmental disorders ( n = 141). To overcome the circular reasoning of aiming to develop a new algorithm and benchmarking to a manually-annotated gold standard, we instead ai...

Neural oscillations are thought to reflect low-level operations that can be used for higher-level cognitive functions. Here, we investigated the role of brain rhythms in the 1–30 Hz range by recording MEG in human participants performing a visual delayed match-to-sample paradigm in which orientation or spatial frequency of sample and probe gratings had to be matched. A cue occurring before or after sample presentation indicated the to-be-matched feature. We demonstrate that alpha/beta power decrease tracks the presentation of the informative cue and indexes faster responses. Moreover, these faster responses coincided with an augmented phase alignment of slow oscillations, as well as phase–amplitude coupling between slow and fast oscillations. Importantly, stimulus decodability was boosted by both low alpha power and high beta power. In summary, we provide support for a comprehensive framework in which different rhythms play specific roles: slow rhythms control input sampling, while alpha (and beta) gates t...