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...

Memory often combines information from different sensory modalities. Animal studies show that synchronized neuronal activity in the theta band (4–8 Hz) binds multimodal associations. Studies with human participants have likewise established that theta-phase synchronization augments the formation of declarative video–tone pair memories. Another form of associative learning, classical fear conditioning, models nondeclarative, emotional memory with distinct neuronal mechanisms. Typical fear-conditioning tasks pair a conditioned stimulus (CS) in one modality with an aversive unconditioned stimulus (US) in another. The present study examines the effects of CS–US synchronization in the theta band on fear memory formation in humans. In a fear generalization procedure, we paired one of five visual gratings of varying orientation (CS) with an aversive auditory US. We modulated the luminance of the CS and the volume of the US at a rate of 4 Hz. To manipulate the synchrony between visual and auditory input during fea...

In Drosophila , molecular pathways affecting longevity have been extensively studied. However, corresponding neurophysiological changes underlying aging-related functional and behavioral deteriorations remain to be fully explored. We examined different motor circuits in Drosophila across the life span and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. In the giant fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex, we observed relatively mild deterioration toward the end of the life span. In contrast, more substantial age-dependent modifications were seen in the plasticity of GF afferent processing, specifically in use dependence and habituation properties. In addition, there were profound changes in different afferent circuits that drive flight motoneuron activities, including flight pattern generation and seizure spike discharges evoked by electroconvulsive stimulation. Importantly, in high-temperat...

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...

A metanalysis identified regulator of G-protein signaling 6 ( RGS6 ) as one of 23 loci with pleiotropic effects on four or more human psychiatric disorders. This finding is significant as it confirms/extends the findings of numerous other studies implicating RGS6 in CNS function and pathology. RGS6 is a highly conserved member of the RGS protein family whose cellular roles are likely affected by mRNA splicing and alternative domain inclusion/exclusion. Indeed, we previously identified multiple RGS6 splice variants predicted to produce 36 distinct protein isoforms containing either long (RGS6L) or short (RGS6S) N-terminal domains, an incomplete or intact GGL domain, and nine alternative C termini. Unfortunately, sequence similarities between the isoforms have made it difficult to confirm their individual existence and/or to determine their unique functions. Here, we developed three RGS6-specific antibodies that recognize all RGS6 protein isoforms (RGS6-fl), the N-terminus of RGS6L isoforms (RGS6-L), and an ...

One of the very first observations made regarding α oscillations (8–14 Hz), is that they increase in power over posterior areas when awake participants close their eyes. Recent work, especially in the context of (spatial) attention, suggests that α activity reflects a mechanism of functional inhibition. However, it remains unclear how eye closure impacts anticipatory α modulation observed in attention paradigms, and how this affects subsequent behavioral performance. Here, we recorded magnetoencephalography (MEG) in 33 human participants performing a tactile discrimination task with their eyes open versus closed. We replicated the hallmarks of previous somatosensory spatial attention studies: α lateralization across the somatosensory cortices as well as α increase over posterior (visual) regions. Furthermore, we found that eye closure leads to (1) reduced task performance; (2) widespread increase in α power; and (3) reduced anticipatory visual α modulation (4) with no effect on somatosensory α lateralizati...

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...