Browsing by Subject "Neurophysiology"

Now showing 1 - 4 of 4
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    Cortical Activation Patterns in Art Making vs. Fine Motor Movement as Measured by EEG
    (2017) Knapp, Kaitlin; Shaikh, Alex; King, Juliet
    This quantitative study explores the differences in cortical activation patterns when subjects create art versus when they engage in a rote motor task. It is hypothesized that a statistically significant difference occurs in cortical activity patterns during art making compared with non- creative rote motor behavior and that such differences can be detected and quantified with the electroencephalogram (EEG.) Ten consenting study subjects (one with formal art training, three with some art experience, and six with no art experience) underwent EEG recording at baseline (multiple measures) and with art making, and also with rote motor tasking. Baseline control recordings showed minimal changes in EEG while art making was associated with a persistent change from baseline of significant direction and amplitude involving both hemispheres, a change that was similar to the persistent change in EEG following rote motor tasks. These preliminary findings suggest that EEG may be a meaningful biomarker for cortical activation in the study of creative arts and points to further exploration using Mobile Brain Body Imaging (MoBI) in experimental designs. This system provides a reproducible, measurable, and quantitative methodology for evaluating brain activity and function in the study of the neuroscientific basis of creative arts, neuroaesthetics, and art therapy.
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    S-Palmitoylation of the sodium channel Nav1.6 regulates its activity and neuronal excitability
    (Elsevier, 2020-05) Pan, Yanling; Xiao, Yucheng; Pei, Zifan; Cummins, Theodore R.; Biology, School of Science
    S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions.
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    The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents
    (American Society for Biochemistry and Molecular Biology, 2020-03) Xu, Yu; Cantwell, Lucas; Molosh, Andrei I.; Plant, Leigh D.; Gazgalis, Dimitris; Fitz, Stephanie D.; Dustrude, Erik T.; Yang, Yuchen; Kawano, Takeharu; Garai, Sumanta; Noujaim, Sami F.; Shekhar, Anantha; Logothetis, Diomedes E.; Thakur, Ganesh A.; Psychiatry, School of Medicine
    G-protein-gated inwardly-rectifying K+ (GIRK) channels are targets of Gi/o-protein-signaling systems that inhibit cell excitability. GIRK channels exist as homotetramers (GIRK2 and GIRK4) or heterotetramers with nonfunctional homomeric subunits (GIRK1 and GIRK3). Although they have been implicated in multiple conditions, the lack of selective GIRK drugs that discriminate among the different GIRK channel subtypes has hampered investigations into their precise physiological relevance and therapeutic potential. Here, we report on a highly-specific, potent, and efficacious activator of brain GIRK1/2 channels. Using a chemical screen and electrophysiological assays, we found that this activator, the bromothiophene-substituted small molecule GAT1508, is specific for brain-expressed GIRK1/2 channels rather than for cardiac GIRK1/4 channels. Computational models predicted a GAT1508-binding site validated by experimental mutagenesis experiments, providing insights into how urea-based compounds engage distant GIRK1 residues required for channel activation. Furthermore, we provide computational and experimental evidence that GAT1508 is an allosteric modulator of channel-phosphatidylinositol 4,5-bisphosphate interactions. Through brain-slice electrophysiology, we show that subthreshold GAT1508 concentrations directly stimulate GIRK currents in the basolateral amygdala (BLA) and potentiate baclofen-induced currents. Of note, GAT1508 effectively extinguished conditioned fear in rodents and lacked cardiac and behavioral side effects, suggesting its potential for use in pharmacotherapy for post-traumatic stress disorder. In summary, our findings indicate that the small molecule GAT1508 has high specificity for brain GIRK1/2 channel subunits, directly or allosterically activates GIRK1/2 channels in the BLA, and facilitates fear extinction in a rodent model.
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    Temporal patterns of synchrony in a pyramidal-interneuron gamma (PING) network
    (AIP, 2021-04) Nguyen, Quynh-Anh; Rubchinsky, Leonid L.; Mathematical Sciences, School of Science
    Synchronization in neural systems plays an important role in many brain functions. Synchronization in the gamma frequency band (30–100 Hz) is involved in a variety of cognitive phenomena; abnormalities of the gamma synchronization are found in schizophrenia and autism spectrum disorder. Frequently, the strength of synchronization is not high, and synchronization is intermittent even on short time scales (few cycles of oscillations). That is, the network exhibits intervals of synchronization followed by intervals of desynchronization. Neural circuit dynamics may show different distributions of desynchronization durations even if the synchronization strength is fixed. We use a conductance-based neural network exhibiting pyramidal-interneuron gamma rhythm to study the temporal patterning of synchronized neural oscillations. We found that changes in the synaptic strength (as well as changes in the membrane kinetics) can alter the temporal patterning of synchrony. Moreover, we found that the changes in the temporal pattern of synchrony may be independent of the changes in the average synchrony strength. Even though the temporal patterning may vary, there is a tendency for dynamics with short (although potentially numerous) desynchronizations, similar to what was observed in experimental studies of neural synchronization in the brain. Recent studies suggested that the short desynchronizations dynamics may facilitate the formation and the breakup of transient neural assemblies. Thus, the results of this study suggest that changes of synaptic strength may alter the temporal patterning of the gamma synchronization as to make the neural networks more efficient in the formation of neural assemblies and the facilitation of cognitive phenomena.