SynCoPa: Visualizing Connectivity Paths and Synapses Over Detailed Morphologies

Brain complexity has traditionally fomented the division of neuroscience into somehow separated compartments; the coexistence of the anatomical, physiological, and connectomics points of view is just a paradigmatic example of this situation. However, there are times when it is important to combine some of these standpoints for getting a global picture, like for fully analyzing the morphological and topological features of a specific neuronal circuit. Within this framework, this article presents SynCoPa, a tool designed for bridging gaps among representations by providing techniques that allow combining detailed morphological neuron representations with the visualization of neuron interconnections at the synapse level. SynCoPa has been conceived for the interactive exploration and analysis of the connectivity elements and paths of simple to medium complexity neuronal circuits at the connectome level. This has been done by providing visual metaphors for synapses and interconnection paths, in combination with the representation of detailed neuron morphologies. SynCoPa could be helpful, for example, for establishing or confirming a hypothesis about the spatial distributions of synapses, or for answering questions about the way neurons establish connections or the relationships between connectivity and morphological features. Last, SynCoPa is easily extendable to include functional data provided, for example, by any of the morphologically-detailed simulators available nowadays, such as Neuron and Arbor, for providing a deep insight into the circuits features prior to simulating it, in particular any analysis where it is important to combine morphology, network topology, and physiology.

Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model

Opioids are widely used for pain relief; however, chronic opioid use causes a paradoxical state of enhanced pain sensitivity, termed “Opioid-induced hyperalgesia (OIH).” Despite the clinical importance of OIH, the detailed mechanism by which it enhances pain sensitivity remains unclear. In this study, we tested whether repeated morphine induces a neuronal circuit polarization in the mouse spinal dorsal horn (SDH). Transgenic mice expressing GFP to neurokinin 1 receptor-expressing neurons (sNK1Rn) and GABAergic interneurons (sGABAn) that received morphine [20 mg/kg, once daily for four consecutive days (i.p.)] developed mechanical hypersensitivity. Repeated morphine altered synaptic strengths in the SDH as a specific cell-type but not in a gender-dependent manner. In sNK1Rn and non-tonic firing neurons, repeated morphine treatment significantly increased frequency of spontaneous excitatory postsynaptic current (sEPSC) and evoked EPSC (eEPSC). In addition, repeated morphine treatment significantly decreased evoked inhibitory postsynaptic current (eIPSC) in sNK1Rn. Conversely, in sGABAn and tonic firing neurons, repeated morphine treatment significantly decreased sEPSC frequency and eEPSC, but had no change of eIPSC in sGABAn. Interestingly, repeated morphine treatment significantly decreased neuronal rheobase of sNK1Rn but had no effect on sGABAn. These findings suggest that spinal neuronal circuit polarization maybe the mechanism of OIH and identify a potential therapeutic mechanism to prevent or treat opioid-induced pain.

Design of Synaptic Neuronal Circuit Based on Memristors

To solve the problems of poor learning efficiency and low accuracy caused by the single fixed synaptic weight in the traditional artificial neural network. On the foundation of the improved memristor model, this paper designs a synaptic neuronal circuit based on the natural memory characteristics of the memristor. This synapse is composed of six memristors. The resistance of the memristor is changed by adding a periodic square wave to update the synaptic weight. This circuit can realize signed synaptic weighting, which has certain linear characteristics. Finally, two synaptic weight update methods are proposed based on this circuit, and the validity of the design is verified through Spice simulation experiments.

Protocerebral Bridge Neurons That Regulate Sleep in Drosophila melanogaster

The central complex is one of the major brain regions that control sleep in Drosophila. However, the circuitry details of sleep regulation have not been elucidated yet. Here, we show a novel sleep-regulating neuronal circuit in the protocerebral bridge (PB) of the central complex. Activation of the PB interneurons labeled by the R59E08-Gal4 and the PB columnar neurons with R52B10-Gal4 promoted sleep and wakefulness, respectively. A targeted GFP reconstitution across synaptic partners (t-GRASP) analysis demonstrated synaptic contact between these two groups of sleep-regulating PB neurons. Furthermore, we found that activation of a pair of dopaminergic (DA) neurons projecting to the PB (T1 DA neurons) decreased sleep. The wake-promoting T1 DA neurons and the sleep-promoting PB interneurons formed close associations. Dopamine 2-like receptor (Dop2R) knockdown in the sleep-promoting PB interneurons increased sleep. These results indicated that the neuronal circuit in the PB, regulated by dopamine signaling, mediates sleep-wakefulness.

Extracellular Calcium Influx Pathways in Astrocyte Calcium Microdomain Physiology

Astrocytes are complex glial cells that play many essential roles in the brain, including the fine-tuning of synaptic activity and blood flow. These roles are linked to fluctuations in intracellular Ca2+ within astrocytes. Recent advances in imaging techniques have identified localized Ca2+ transients within the fine processes of the astrocytic structure, which we term microdomain Ca2+ events. These Ca2+ transients are very diverse and occur under different conditions, including in the presence or absence of surrounding circuit activity. This complexity suggests that different signalling mechanisms mediate microdomain events which may then encode specific astrocyte functions from the modulation of synapses up to brain circuits and behaviour. Several recent studies have shown that a subset of astrocyte microdomain Ca2+ events occur rapidly following local neuronal circuit activity. In this review, we consider the physiological relevance of microdomain astrocyte Ca2+ signalling within brain circuits and outline possible pathways of extracellular Ca2+ influx through ionotropic receptors and other Ca2+ ion channels, which may contribute to astrocyte microdomain events with potentially fast dynamics.

Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans

Understanding the molecular events that regulate cell pluripotency versus acquisition of differentiated somatic cell fate is fundamentally important. Studies in Caenorhabditis elegans demonstrate that knockout of the germline-specific translation repressor gld-1 causes germ cells within tumorous gonads to form germline-derived teratoma. Previously we demonstrated that endoplasmic reticulum (ER) stress enhances this phenotype to suppress germline tumor progression(Levi-Ferber et al., 2015). Here, we identify a neuronal circuit that non-autonomously suppresses germline differentiation and show that it communicates with the gonad via the neurotransmitter serotonin to limit somatic differentiation of the tumorous germline. ER stress controls this circuit through regulated inositol requiring enzyme-1 (IRE-1)-dependent mRNA decay of transcripts encoding the neuropeptide FLP-6. Depletion of FLP-6 disrupts the circuit’s integrity and hence its ability to prevent somatic-fate acquisition by germline tumor cells. Our findings reveal mechanistically how ER stress enhances ectopic germline differentiation and demonstrate that regulated Ire1-dependent decay can affect animal physiology by controlling a specific neuronal circuit.

A model of rapid homeostatic plasticity accounts for hidden, long-lasting changes in a neuronal circuit after exposure to high potassium.

Neural circuits must both function reliably and flexibly adapt to changes in their environment. We studied how both biological neurons and computational models respond to high potassium concentrations. Pyloric neurons of the crab stomatogastric ganglion (STG) initially become quiescent, then recover spiking activity in high potassium saline. The neurons retain this adaptation and recover more rapidly in subsequent high potassium applications, even after hours in control saline. We constructed a novel activity-dependent computational model that qualitatively captures these results. In this model, regulation of conductances is gated on and off depending on how far the neuron is from its target activity. This allows the model neuron to retain a trace of past perturbations even after it returns to its target activity in control conditions. Thus, perturbation, followed by recovery of normal activity, can hide cryptic changes in neuronal properties that are only revealed by subsequent perturbations.

GUIDING ASPECTS OF ISLAMIC EXISTENTIAL-COGNITIVE BEHAVIOUR THERAPY FOR EXISTENTIAL DEPRESSION

The CoVid-19 pandemic had again activated the neuronal circuit on our existential crisis as human beings asking basic existential questions: Where were we from, who are we, why are we here, how we supposedly should live here and where are we going? - Instinctively it appears evidently in the soul while facing threats that may lead to death like the pandemic exposes us to. This study critically explores and analyses through content analysis method on available published ‘Islamic’ documents, which are purposively sampled based on relevancy to the existence. We shared what we found related to existential psychotherapy using cognitive behavior therapy for depressed Muslim clients in supporting the current call for integrating Islamic teachings and practice. Mainly, being intersubjective is very crucial for therapists’ competency because Muslim clients are from diverse Islamic backgrounds.