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...

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...

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...

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...

In the article, “Induction of Short-Term Sensitization by an Aversive Chemical Stimulus in Zebrafish Larvae,” by Adam C. Roberts, Joseph B. Alzagatiti, Duy T. Ly, Julia M. Chornak, Yuqi Ma, Asif Razee, Gohar Zavradyan, Umair Khan, Julia Lewis, Aishwarya Natarajan, Alisher Baibussinov, Jasmine Emtage, Meghna Komaranchath, Jared Richards, Michelle Hoang, Jason Alipio, Emma Laurent, Amit …

Despite significant progress in understanding neural coding, it remains unclear how the coordinated activity of large populations of neurons relates to what an observer actually perceives. Since neurophysiological differences must underlie differences among percepts, differentiation analysis —quantifying distinct patterns of neurophysiological activity—has been proposed as an “inside-out” approach that addresses this question. This methodology contrasts with “outside-in” approaches such as feature tuning and decoding analyses, which are defined in terms of extrinsic experimental variables. Here, we used two-photon calcium imaging in mice of both sexes to systematically survey stimulus-evoked neurophysiological differentiation (ND) in excitatory neuronal populations in layers (L)2/3, L4, and L5 across five visual cortical areas (primary, lateromedial, anterolateral, posteromedial, and anteromedial) in response to naturalistic and phase-scrambled movie stimuli. We find that unscrambled stimuli evoke greater ...

Humans rely on precise proprioceptive feedback from our muscles, which is important in both the acquisition and execution of movements, to perform daily activities. Somatosensory input from the body shapes motor learning through central processes, as demonstrated for tasks using the arm, under active (self-generated) and passive conditions. Presently, we investigated whether passive movement training of the ankle increased proprioceptive acuity (psychophysical experiment) and whether it changed the peripheral proprioceptive afferent signal (microneurography experiment). In the psychophysical experiment, the ankle of 32 healthy human participants was moved passively using pairs of ramp-and-hold movements in different directions. In a pretraining test, participants made judgements about the movement direction in a two-alternative forced choice paradigm. Participants then underwent passive movement training, but only half were cued for learning, where a reference position was signaled by a sound and the parti...

Attention-deficit/hyperactivity disorder (ADHD) in adults is understudied, especially regarding neural mechanisms such as oscillatory control of attention sampling. We report an electroencephalography (EEG) study of such cortical mechanisms, in ADHD-diagnosed adults during administration of Test of Variables of Attention (TOVA), a gold-standard continuous performance test for ADHD that measures the ability to sustain attention and inhibit impulsivity. We recorded 53 adults (28 female, 25 male, aged 18–60), and 18 matched healthy controls, using 128-channel EEG. We analyzed sensor-space features established as neural correlates of attention: timing-sensitivity and phase-synchrony of response activations, and event-related (de)synchronization (ERS/D) of α and θ frequency band activity; in frontal and parietal scalp regions. TOVA test performance significantly distinguished ADHD adults from neurotypical controls, in commission errors, response time variability (RTV) and d′ (response sensitivity). The ADHD gro...

Fear and anxiety can be described as emotional and physical responses to predictable and unpredictable threats. While the amygdala is necessary for context and cued fear conditioning, the bed nucleus of the stria terminalis (BNST) is important for anxiety-like behavior and conditioned responses to diffuse and/or unpredictable threats. However, we still lack knowledge about how the BNST and amygdala nuclei act in coordination. Moreover, the incidence of anxiety disorders and posttraumatic stress disorder (PTSD) is substantially higher in women than in men, but most studies of fear conditioning are conducted in male rodents. Here, we asked whether the BNST and the lateral, basal, and central nuclei of the amygdala are active during the expression of fear conditioning in male and female rats using FOS immunohistochemistry. We first show that the BNST is indeed involved in context fear expression in males, but not in females. The lateral amygdala was active in both sexes during context fear expression. We next...

Parvalbumin (PV)-producing neurons are the largest subpopulation of cortical GABAergic interneurons, which mediate lateral, feedforward, and feedback inhibition in local circuits and modulate the activity of pyramidal neurons. Clarifying the specific connectivity between pyramidal and PV neurons is essential for understanding the role of PV neurons in local circuits. In the present study, we visualized somas and dendrites of PV neurons using transgenic mice in which PV neurons specifically express membrane-targeted GFP, and intracellularly labeled local axons of 26 pyramidal neurons in layers 2–6 in acute slices of the motor-associated cortex from transgenic mice. We mapped morphologically distribution of inputs from a pyramidal neuron to PV neurons based on contact sites (appositions) between the axons from an intracellularly filled pyramidal neuron and the dendrites of PV neurons. Layer 6 corticothalamic (CT)-like pyramidal neurons formed appositions to PV neurons at a significantly higher rate than othe...