Gordon Holmes syndrome (GHS) is a neurological disorder associated with neuroendocrine, cognitive, and motor impairments with corresponding neurodegeneration. Mutations in the E3 ubiquitin ligase RNF216 are strongly linked to GHS. Previous studies show that deletion of Rnf216 in mice led to sex-specific neuroendocrine dysfunction due to disruptions in the hypothalamic-pituitary-gonadal axis. To address RNF216 action in cognitive and motor functions, we tested Rnf216 knockout (KO) mice in a battery of motor and learning tasks for a duration of one year. Although male and female KO mice did not demonstrate prominent motor phenotypes, KO females displayed abnormal limb clasping. KO mice also showed age-dependent strategy and associative learning impairments with sex-dependent alterations of microglia in the hippocampus and cortex. Additionally, KO males but not females had more negative resting membrane potentials in the CA1 hippocampus without any changes in miniature excitatory postsynaptic current (mEPSC) ...

The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in their connection strength with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert distinct influences on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1 in male and female mice, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that M1 and S1 dually innervate SPNs and FSIs, however there is a consistent bia...

Voluntary motor control is thought to be predicated on the ability to efficiently integrate and process somatosensory afferent information. However, current approaches in the field of motor control have not factored in objective markers of how the brain tracks incoming somatosensory information. Here, we asked whether motor performance relates with such markers obtained with an analysis of the coupling between peripheral kinematics and cortical oscillations during continuous movements, best known as corticokinematic coherence (CKC). Motor performance was evaluated by measuring both gross and fine motor skills using the Box and Blocks Test (BBT) and the Purdue Pegboard Test (PPT), respectively, and with a biomechanics measure of coordination. Sixty-one participants completed the BBT, while equipped with electroencephalography and electromyography, and the PPT. We evaluated CKC, from the signals collected during the BBT, as the coherence between movement rhythmicity and brain activity, and coordination as th...

Declaring the 1990's as The Decade of the Brain put the field of neuroscience at the forefront of public attention, with the nervous system becoming a subject of increasing interest in popular media. Although this has generally brought large swaths of the public closer to neuroscience, most current research is published and disseminated in a single language: English. This is unsurprising as English is indeed the lingua franca in scientific circles, but people around the world communicate in many other languages. To make neuroscience accessible to a larger audience, we share an initiative to translate the Knowing Neurons platform into a second language: Spanish. This collaborative project integrates Humanities and STEM academic programs to make use of bilingual university students, in association with professional linguists and neuroscientists, to translate scientific content into a relatable format to Spanish speakers regardless of their country of origin. The translation effort was piloted within the fram...

Humans use tactile feedback to perform skillful manipulation. When tactile sensory feedback is unavailable, for instance, if the fingers are anesthetized, dexterity is severely impaired. Imaging the deformation of the finger pad skin when in contact with a transparent plate provides information about the tactile feedback received by the central nervous system. Indeed, skin deformations are transduced into neural signals by the mechanoreceptors of the finger pad skin. Understanding how this feedback is used for active object manipulation would improve our understanding of human dexterity. In this paper, we present a new device for imaging the skin of the finger pad of one finger during manipulation performed with a precision grip. The device’s mass (300 g) makes it easy to use during unconstrained dexterous manipulation. Using this device, we reproduced the experiment performed in Delhaye et al. 2021a. We extracted the strains aligned with the object’s movement, i.e., the vertical strains in the ulnar and r...

Stereotypical isocortical tau protein pathology along the Braak-Stages has been described as an instigator of neurodegeneration in Alzheimer's Disease (AD). Less is known about tau pathology in motor regions, although higher-order motor deficits such as praxis dysfunction are part of the clinical description. Here, we examined how tau pathology in cytoarchitectonically mapped regions of the primary and higher-order motor network in comparison to primary visual and sensory regions varies across the clinical spectrum of AD. We analyzed tau PET scans from the ADNI-cohort in patients with mild cognitive impairment (MCI; N  = 84) and dementia of the Alzheimer's Disease type (DAD; N  = 25). Additionally, an amyloid-negative sample of healthy older individuals (HC; N  = 26) were included. Standard-uptake ratio values (SUVR) were extracted in native space from the left and the right hemispheres. A repeated measurement analysis of variance was conducted to assess the effect of diagnostic disease category on tau pat...

Dysfunction in the gene SCN2A , which encodes the voltage-gated sodium channel Nav1.2, is strongly associated with neurodevelopmental disorders including autism spectrum disorder and intellectual disability (ASD/ID). This dysfunction typically manifests in these disorders as a haploinsufficiency, where loss of one copy of a gene cannot be compensated for by the other allele. Scn2a haploinsufficiency affects a range of cells and circuits across the brain, including associative neocortical circuits that are important for cognitive flexibility and decision-making behaviors. Here, we tested whether Scn2a haploinsufficiency has any effect on a dynamic foraging task that engages such circuits. Scn2a +/− mice and wild-type (WT) littermates were trained on a choice behavior where the probability of reward between two options varied dynamically across trials and where the location of the high reward underwent uncued reversals. Despite impairments in Scn2a -related neuronal excitability, we found that both male and ...

Spatial memories are represented by hippocampal place cells during navigation. This spatial code is dynamic, undergoing changes across time, known as representational drift, and across changes in internal state, even while navigating the same spatial environment with consistent behavior. A dynamic code may provide the hippocampus a means to track distinct epochs of experience that occur at different times or during different internal states and update spatial memories. Changes to the spatial code include place fields (PFs) that remap to new locations and place fields that vanish, while others are stable. However, what determines place field fate across epochs remains unclear. We measured the lap-by-lap properties of place cells in mice during navigation for a block of trials in a rewarded virtual environment. We then determined the position of the place fields in another block of trials in the same spatial environment either separated by a day (a distinct temporal epoch) or during the same session but with...

Accurately and quantitatively describing mouse behavior is an important area. Although advances in machine learning have made it possible to track their behaviors accurately, reliable classification of behavioral sequences or syllables remains a challenge. In this study, we present a novel machine learning approach, called SaLSa (a combination of semi-automatic labeling and long short-term memory-based classification), to classify behavioral syllables of mice exploring an open field. This approach consists of two major steps. First, after tracking multiple body parts, spatial and temporal features of their egocentric coordinates are extracted. A fully automated unsupervised process identifies candidates for behavioral syllables, followed by manual labeling of behavioral syllables using a graphical user interface (GUI). Second, a long short-term memory (LSTM) classifier is trained with the labeled data. We found that the classification performance was marked over 97%. It provides a performance equivalent to...

The ventromedial motor thalamus (VM) is implicated in multiple motor functions and occupies a central position in the cortico-basal ganglia-thalamocortical loop. It integrates glutamatergic inputs from motor cortex (MC) and motor-related subcortical areas, and it is a major recipient of inhibition from basal ganglia. Previous in vitro experiments performed in mice showed that dopamine depletion enhances the excitability of thalamocortical (TC) neurons in VM due to reduced M-type potassium currents. To understand how these excitability changes impact synaptic integration in vivo , we constructed biophysically detailed mouse VM TC model neurons fit to normal and dopamine-depleted conditions, using the NEURON simulator. These models allowed us to assess the influence of excitability changes with dopamine depletion on the integration of synaptic inputs expected in vivo . We found that VM neuron models in the dopamine-depleted state showed increased firing rates with the same synaptic inputs. Synchronous bursti...