Restoration of lost function following a nervous system injury is limited in adulthood as the regenerative capacity of nervous system declines with age. Pharmacological approaches have not been very successful in alleviating the consequences of nervous system injury. On the contrary, physical activity and rehabilitation interventions are often beneficial to improve the health conditions in the patients with neuronal injuries. Using touch neuron circuit of Caenorhabditis elegans , we investigated the role of physical exercise in the improvement of functional restoration after axotomy. We found that a swimming session of 90 minutes following the axotomy of Posterior Lateral Microtubule (PLM) neuron can improve functional recovery in larval and adult stage animals. In older age, multiple exercise sessions were required to enhance the functional recovery. Genetic analysis of axon regeneration mutants showed that exercise-mediated enhancement of functional recovery depends on the ability of axon to regenerate. ...

Prolonged stress induces neural maladaptations in mesolimbic dopamine (DA) system and produces emotional and behavioral disorders. However, the effects of stress on activity of DA neurons are diverse and complex that hinge on the type, duration, intensity, and controllability of stressors. Here, controlling the duration, intensity, and type of the stressors to be identical, we observed effects of stressor controllability on the activity of substantia nigra compacta (SNc) DA neurons in mice. We found that both lack and loss of control over shock enhance the basal activity and intrinsic excitability of SNc DA neurons via modulation of Ih current, but not via corticosterone serum level. Moreover, loss of control over shock produces more significant enhancement in the basal activity of SNc DA neurons than that produced shock per se, and therefore attenuates the response to natural reward. This attenuation can be reversed by control over shock. These results indicate that although chronic stress per se tends to...

Pediatric traumatic brain injury (TBI) results in heightened risk for social deficits that can emerge during adolescence and adulthood. A moderate TBI in male and female rats on postnatal day 11 (equivalent to children below the age of 3) resulted in impairments in social novelty recognition, defined as the preference for interacting with a novel rat compared to a familiar rat, but not sociability, defined as the preference for interacting with a rat compared to an object in the three-chamber test when tested at 4-weeks (adolescence) and 8-weeks (adulthood) post-injury. The deficits in social recognition were not accompanied by deficits in novel object recognition memory and were associated with a decrease in the frequency of spontaneous inhibitory postsynaptic currents (IPSC) recorded from pyramidal neurons within layer II/III of the medial prefrontal cortex (mPFC). Whereas TBI did not affect the expression of oxytocin (OXT) or the oxytocin Receptor (OXT-R) mRNAs in the hypothalamus and mPFC respectively,...

The long cellular architecture of neurons requires regulation in part through transport and anchoring events to distribute intracellular organelles. During development, cellular and sub-cellular events such as organelle additions and their recruitment at specific sites on the growing axons occur over different time scales and often show inter-animal variability thus making it difficult to identify specific phenomena in population averages. To measure the variability in sub-cellular events such as organelle positions, we developed a microfluidic device to feed and immobilize C. elegans for high-resolution imaging over several days. The microfluidic device enabled long-term imaging of individual animals and allowed us to investigate organelle density using mitochondria as a testbed in a growing neuronal process in vivo . Sub-cellular imaging of an individual neuron in multiple animals, over 36 hours in our microfluidic device, shows the addition of new mitochondria along the neuronal process and an increase ...

Alpha oscillations in sensory cortex, under frontal control, desynchronize during attentive preparation. Here, in a selective attention study with simultaneous EEG in humans of either sex, we first demonstrate that diminished anticipatory alpha synchrony between the mid-frontal region of the dorsal attention network and ventral visual sensory cortex (frontal-sensory synchrony (FSS)) significantly correlates with greater task performance. Then, in a double-blind, randomized controlled study in healthy adults, we implement closed-loop neurofeedback of the anticipatory alpha FSS signal over ten days of training. We refer to this closed-loop experimental approach of rapid neurofeedback (NF) integrated within a cognitive task as cognitive neurofeedback (cNF). We show that cNF results in significant trial-by-trial modulation of the anticipatory alpha FSS measure during training, concomitant plasticity of stimulus-evoked alpha/theta responses, as well as transfer of benefits to response time improvements on a sta...

Misophonia is a common disorder characterized by the experience of strong negative emotions of anger and anxiety in response to certain everyday sounds, such as those generated by other people eating, drinking and breathing. The commonplace nature of these ‘trigger’ sounds makes misophonia a devastating disorder for sufferers and their families. How such innocuous sounds trigger this response is unknown. Since most trigger sounds are generated by orofacial movements (e.g. chewing) in others, we hypothesized that the mirror neuron system related to orofacial movements could underlie misophonia. We analysed resting state fMRI (rs-fMRI) connectivity (N=33, 16 females) and sound-evoked fMRI responses (N=42, 29 females) in misophonia sufferers and controls. We demonstrate that, compared to controls, the misophonia group show no difference in auditory cortex responses to trigger sounds, but do show: (i) stronger rs-fMRI connectivity between both auditory and visual cortex and the ventral pre-motor cortex respons...

Protein phosphatase 2B (PP2B) is critical for synaptic plasticity and learning, but the molecular mechanisms involved remain unclear. Here we identified different types of proteins that interact with PP2B, among which structural proteins of the postsynaptic densities (PSDs) of Purkinje cells (PCs) in mice of either se. Deleting PP2B reduced expression of PSD proteins and the relative thickness of PSD at parallel fiber to PC synapses, whereas re-expression of inactive PP2B partly restored the impaired distribution of nanoclusters of PSD proteins, together indicating a structural role of PP2B. In contrast, lateral mobility of surface glutamate receptors solely depended on PP2B phosphatase activity. Finally, the level of motor learning co-varied with both the enzymatic and non-enzymatic function of PP2B. Thus, PP2B controls synaptic function and learning both through its action as a phosphatase and as a structural protein facilitating synapse integrity. SIGNIFICANCE STATEMENT Phosphatases are generally con...

The adult olfactory epithelium (OE) regenerates sensory neurons and non-sensory supporting cells from resident stem cells after injury. How supporting cells contribute to OE regeneration remains largely unknown. In this study, we elucidated a novel role of Ym2 (also known as Chil4 or Chi3l4), a chitinase-like protein expressed in supporting cells, in regulating regeneration of the injured OE in vivo in both male and female mice and cell proliferation/differentiation in OE colonies in vitro . We found that Ym2 expression was enhanced in supporting cells after OE injury. Genetic knockdown of Ym2 in supporting cells attenuated recovery of the injured OE while Ym2 overexpression by lentiviral infection accelerated OE regeneration. Similarly, Ym2 bidirectionally regulated cell proliferation and differentiation in OE colonies. Furthermore, anti-inflammatory treatment reduced Ym2 expression and delayed OE regeneration in vivo and cell proliferation/differentiation in vitro , which were counteracted by Ym2 overexp...

The ventral visual stream of the human brain is subdivided into patches with categorical stimulus preferences, like faces or scenes. However, the functional organization within these areas is less clear. Here, we used functional magnetic resonance imaging and vertex-wise tuning models to independently probe spatial and face-part preferences in the inferior occipital gyrus (IOG) of healthy adult males and females. The majority of responses were well explained by Gaussian population tuning curves for both retinotopic location and the preferred relative position within a face. Parameter maps revealed a common gradient of spatial and face-part selectivity, with the width of tuning curves drastically increasing from posterior to anterior IOG. Tuning peaks clustered more idiosyncratically, but were also correlated across maps of visual and face-space. Preferences for the upper visual field went along with significantly increased coverage of the upper half of the face, matching recently discovered biases in human...

Voices are arguably among the most relevant sounds in humans’ everyday life, and several studies have suggested the existence of voice-selective regions in the human brain. Despite two decades of research, defining the human brain regions supporting voice recognition remains challenging. Moreover, whether neural selectivity to voices is merely driven by acoustic properties specific to human voices (e.g., spectrogram, harmonicity), or whether it also reflects a higher-level categorization response is still under debate. Here, we objectively measured rapid automatic categorization responses to human voices with fast periodic auditory stimulation (FPAS) combined with electroencephalography (EEG). Participants were tested with stimulation sequences containing heterogeneous non-vocal sounds from different categories presented at 4 Hz (i.e., four stimuli/s), with vocal sounds appearing every three stimuli (1.333 Hz). A few minutes of stimulation are sufficient to elicit robust 1.333-Hz voice-selective focal brai...