Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signaling, which play a role in salience modulation. Consequently, hippocampal neural disinhibition may contribute to impairments in fear conditioning and salience modulation reported in schizophrenia. Therefore, we examined the effect of ventral hippocampus (VH) disinhibition in male rats on fear conditioning and salience modulation, as reflected by latent inhibition (LI), in a conditioned emotional response (CER) procedure. A flashing light was used as the conditioned stimulus (CS), and conditioned suppression was used to index conditioned fear. In experiment 1, VH disinhibition via infusion of the GABA-A receptor antagonist picrotoxin before CS pre-exposure and conditioning markedly reduced fear conditioning to both t...

The neurophysiological processes reflecting body illusions such as the rubber hand remain debated. Previous studies investigating the neural responses evoked by the illusion-inducing stimulation have provided diverging reports as to when these responses reflect the illusory state of the artificial limb becoming embodied. One reason for these diverging reports may be that different studies contrasted different experimental conditions to isolate potential correlates of the illusion, but individual contrasts may reflect multiple facets of the adopted experimental paradigm and not just the illusory state. To resolve these controversies, we recorded EEG responses in human participants and combined multivariate (cross-)classification with multiple Illusion and non-Illusion conditions. These conditions were designed to probe for markers of the illusory state that generalize across the spatial arrangements of limbs or the specific nature of the control object (a rubber hand or participant’s real hand), hence which...

The major pathology in Parkinson’s disease (PD) is neuron injury induced by degeneration of dopaminergic neurons and the activation of microglial cells. The objective of this study is to determine the effect and mechanism of miR-132-3p in regulating neuroinflammation and the degeneration of dopaminergic neuron in PD. The expressions of miR-132-3p in brain tissues of PD patients, lipopolysaccharide (LPS)-induced BV-2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models were detected. The effect of miR-132-3p and GLRX in cell viability, apoptosis and inflammation was verified in BV-2 cells. The activation of Iba1 in substantia nigra pars compacta (SNc) and the loss of tyrosine hydroxylase were detected in PD mouse models and the mobility of mouse models was assessed as well. The targeting relationship between miR-132-3p and GLRX was confirmed by RNA immunoprecipitation (RIP) and dual luciferase reporter gene assay. Elevated expression of miR-132-3p and decreased expression of...

Information transfer and integration in the brain occurs at chemical synapses and is mediated by the fusion of synaptic vesicles filled with neurotransmitter. Synaptic vesicle dynamic spatial organization regulates synaptic transmission as well as synaptic plasticity. Because of their small size, synaptic vesicles require electron microscopy (EM) for their imaging, and their analysis is conducted manually. The manual annotation and segmentation of the hundreds to thousands of synaptic vesicles, is highly time consuming and limits the throughput of data collection. To overcome this limitation, we built an algorithm, mainly relying on convolutional neural networks (CNNs), capable of automatically detecting and localizing synaptic vesicles in electron micrographs. The algorithm was trained on murine synapses but we show that it works well on synapses from different species, ranging from zebrafish to human, and from different preparations. As output, we provide the vesicle count and coordinates, the nearest ne...

Over half of all spinal cord injuries (SCIs) are cervical, which can lead to paralysis and respiratory compromise, causing significant morbidity and mortality. Effective treatments to restore breathing after severe upper cervical injury are lacking; thus, it is imperative to develop therapies to address this. Epidural stimulation has successfully restored motor function after SCI for stepping, standing, reaching, grasping, and postural control. We hypothesized that closed-loop stimulation triggered via healthy hemidiaphragm EMG activity has the potential to elicit functional neuroplasticity in spinal respiratory pathways after cervical SCI (cSCI). To test this, we delivered closed-loop, electrical, epidural stimulation (CLES) at the level of the phrenic motor nucleus (C4) for 3 d after C2 hemisection (C2HS) in freely behaving rats. A 2 × 2 Latin Square experimental design incorporated two treatments, C2HS injury and CLES therapy resulting in four groups of adult, female Sprague Dawley rats: C2HS + CLES ( n...

Oxytocin (Oxt) controls reproductive physiology and various kinds of social behaviors, but the exact contribution of Oxt to different components of parental care still needs to be determined. Here, we illustrate the neuroanatomical relations of the parental nurturing-induced neuronal activation with magnocellular Oxt neurons and fibers in the medial preoptic area (MPOA), the brain region critical for parental and alloparental behaviors. We used genetically-targeted mouse lines for Oxt , Oxt receptor ( Oxtr ), vasopressin receptor 1a ( Avpr1a ), vasopressin receptor 1b ( Avpr1b ), and thyrotropin-releasing hormone ( Trh ) to systematically examine the role of Oxt-related signaling in pup-directed behaviors. The Oxtr - Avpr1a - Avpr1b triple knock-out (TKO), and Oxt - Trh - Avpr1a - Avpr1b quadruple KO (QKO) mice were grossly healthy and fertile, except for their complete deficiency in milk ejection and modest deficiency in parturition secondary to maternal loss of the Oxt or Oxtr gene. In our minimal stress...

Autonomic parasympathetic preganglionic neurons (PGNs) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be because of recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within Lamina VII, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters. Additional morphologic analysis separated these neuronal classes into parasympathetic preganglionic populations (PGN) and a fast-firing interneuronal population. Kv3 channels are voltage-gated potassium channels (Kv) that allow fast and precise firing of neurons. We found that blockade of Kv3 channels by tetraethylammonium (TEA) reduced neuronal firing frequency and isolated high-voltage-activated Kv currents in the fast-firing population but had no effect in PGN populations. Furthermore, Kv3 blockade potentiated the local and descending inhi...

Stereoscopic vision enables the perception of depth. To study the brain mechanisms behind stereoscopic vision using noninvasive brain imaging (magnetic resonance brain imaging; MRI), scientists need to reproduce the independent views of the left and right eyes in the brain scanner using “dichoptic” displays. However, high-quality dichoptic displays are technically challenging and costly to implement in the MRI scanner. The novel miniature stereoscope system (“MRI stereoscope”) is an affordable and open-source tool that displays high-quality dichoptic images inside the MRI scanner. The MRI stereoscope takes advantage of commonly used display equipment, the MRI head coil, and a display screen. To validate the MRI stereoscope, binocular disparity stimuli were presented in a 3T MRI scanner while neural activation was recorded using functional MRI in six human participants. The comparison of large binocular disparities compared with disparities close to zero evoked strong responses across dorsal and ventral ext...

The aging brain undergoes structural changes even in very healthy individuals. Quantifying these changes could help disentangle pathologic changes from those associated with the normal human aging process. Using longitudinal magnetic resonance imaging (MRI) data from 227 carefully selected healthy human cohort with age ranging from 50 to 80 years old at baseline scan, we quantified age-related volumetric changes in the brain of healthy human older adults. Longitudinally, the rates of tissue loss in total gray matter (GM) and white matter (WM) were 2497.5 and 2579.8 mm3 per year, respectively. Across the whole brain, the rates of GM decline varied with regions in the frontal and parietal lobes having faster rates of decline, whereas some regions in the occipital and temporal lobes appeared relatively preserved. In contrast, cross-sectional changes were mainly observed in the temporal-occipital regions. Similar longitudinal atrophic changes were also observed in subcortical regions including thalamus, hippoc...

Spinal cord injury (SCI) is a devastating condition. Splenectomy may play a protective role in the development of SCI. However, little is known about whether the timing of splenectomy affects the outcome after SCI. Investigation into splenectomy after SCI would provide insight into how the timing can be selected following SCI to improve neurologic outcomes. Rats were randomized into a sham group, a nonsplenectomized group (NonSPX), four splenectomized groups with the surgery performed immediately, 6 h, 12 h, and 24 h after SCI (SPX0, SPX6, SPX12, and SPX24, respectively). Rats were subjected to severe contusive SCI at the level of the third thoracic vertebra. At different time points following SCI, Basso, Beattie, and Bresnahan (BBB) score was used to assess the recovery of injury. The animals in each group were randomly selected for tissue collection at days 3, 14, and 28 after surgery. Then, immunohistochemistry of immunologic cells was performed and inflammatory mediators were determined. Our study show...