The Predominance of Electric Transport in Synaptic Transmission

The quantitative description of the motion of neurotransmitters in the synaptic cleft appears to be one of the most difficult problems in the modeling of synapses. Here we show in contradiction to the common view, that this process is merely governed by electric transport than diffusion forces

Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility.

Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs) with two different geometries (sphere and rod) and quantum dots (QDs) with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA), and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach

Imaging striatal dopamine release using a nongenetically encoded near infrared fluorescent catecholamine nanosensor.

Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000-1300 nm), near infrared catecholamine nanosensor (nIRCat). We demonstrate that nIRCats can be used to measure electrically and optogenetically evoked dopamine release in brain tissue, revealing hotspots with a median size of 2 µm. We also demonstrated that nIRCats are compatible with dopamine pharmacology and show D2 autoreceptor modulation of evoked dopamine release, which varied as a function of initial release magnitude at different hotspots. Together, our data demonstrate that nIRCats and other nanosensors of this class can serve as versatile synthetic optical tools to monitor neuromodulatory neurotransmitter release with high spatial resolution

Computational Astrocyence: Astrocytes encode inhibitory activity into the frequency and spatial extent of their calcium elevations

Deciphering the complex interactions between neurotransmission and astrocytic $Ca^{2+}$ elevations is a target promising a comprehensive understanding of brain function. While the astrocytic response to excitatory synaptic activity has been extensively studied, how inhibitory activity results to intracellular $Ca^{2+}$ waves remains elusive. In this study, we developed a compartmental astrocytic model that exhibits distinct levels of responsiveness to inhibitory activity. Our model suggested that the astrocytic coverage of inhibitory terminals defines the spatial and temporal scale of their $Ca^{2+}$ elevations. Understanding the interplay between the synaptic pathways and the astrocytic responses will help us identify how astrocytes work independently and cooperatively with neurons, in health and disease.Comment: 4 pages, 3 figures, IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI '19

Local and global spontaneous calcium events regulate neurite outgrowth and onset of GABAergic phenotype during neural precursor differentiation

Neural stem cells can generate in vitro progenitors of the three main cell lineages found in the CNS. The signaling pathways underlying the acquisition of differentiated phenotypes in these cells are poorly understood. Here we tested the hypothesis that Ca2+ signaling controls differentiation of neural precursors. We found low-frequency global and local Ca2+ transients occurring predominantly during early stages of differentiation. Spontaneous Ca2+ signals in individual precursors were not synchronized with Ca2+ transients in surrounding cells. Experimentally induced changes in the frequency of local Ca2+signals and global Ca2+ rises correlated positively with neurite outgrowth and the onset of GABAergic neurotransmitter phenotype, respectively. NMDA receptor activity was critical for alterations in neuronal morphology but not for the timing of the acquisition of the neurotransmitter phenotype. Thus, spontaneous Ca2+ signals are an intrinsic property of differentiating neurosphere-derived precursors. Their frequency may specify neuronal morphology and acquisition of neurotransmitter phenotype

Neurochemical substrates and neuroanatomical generators of the event-related P300

The present review focuses on the current knowledge of the neurochemical processes and neuronal structures involved in the generation of P300. The increasing knowledge in this area facilitates the physiological interpretation of P300 findings as well as the link between P300 research and other research findings in biological psychiatry. Concerning the question of neurochemical substrates, the glutamatergic, GABAergic, cholinergic, noradrenergic, dopaminergic and serotonergic influences on P300 are reviewed. The knowledge of the generating structures of P300 is summarized from intracranial studies, magnetoencephalographic investigations, lesion and animal studies

Pain Perception: Investigating Links Between Pain Transmission and CCK(+) Neurons, with Regard to the Opioid Crisis

With dependence on opioids, such as codeine, morphine, and heroin, steadily increasing amongst the American public, the withdrawal symptoms associated with disuse are receiving much more attention. Our research identifies neurons that are implicated in the hyperanalgesic response to the cessation of opiate medication after dependence has been established. These neurons, identified by the cholecystokinin protein (CCK), are localized in regions of the central nervous system that are responsible for transducing painful signals from the periphery to the brain. In particular, our research focuses on the substantia gelatinosa of the spinal cord and the trigeminal nucleus within the brain stem; the spinal cord is responsible for transmitting painful signals from below the shoulders, and the trigeminal nucleus is responsible for transmitting pain from above the shoulders. Our research supports the hypothesis that neurons with high levels of CCK expression (CCK(+) neurons) are involved in the transmission of pain from the periphery, where the pain occurs, to the brain, where it is perceived. We did not find that the CCK(+) neurons communicate through GABA neurotransmission, and we will continue researching how these neurons communicate, as well as the implications they have on the modulation of pain by opiate use/disuse

Increased bradykinesia in Parkinson’s disease with increased movement complexity: elbow flexion-extension movements

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson’s disease (PD) patients. The functional scheme of the basal ganglia (BG)–thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms