The appropriate growth of the neurons, accurate organization of their synapses, and successful neurotransmission are indispensable for sensorimotor activities. These processes are highly dynamic and tightly regulated. Extensive genetic, molecular, physiological, and behavioral studies have identified many molecular candidates and investigated their roles in various neuromuscular processes.
View Article and Find Full Text PDFPannexins are single-membrane large-pore channels that release ions and ATP upon activation. Three isoforms of pannexins 1, 2, and 3, perform diverse cellular roles and differ in their pore lining residues. In this study, we report the cryo-EM structure of pannexin 3 at 3.
View Article and Find Full Text PDFAim: Acetylcholine release is vital in the pacing of theta rhythms in the hippocampus. The subiculum is the output region of the hippocampus with different neuronal subtypes that generate theta oscillations during arousal and rapid eye movement sleep. The combination of intrinsic resonance in the hippocampal neurons and the periodic excitation of hippocampal excitatory and inhibitory neurons by cholinergic pathway drives theta oscillations.
View Article and Find Full Text PDFTREK-1, a two-pore domain potassium channel, responds to ischemic levels of intracellular lactate and acidic pH to provide neuroprotection. There are two splice variants of hTREK1: the shorter splice variant having a shorter N-terminus compared with the full-length hTREK1 with similar C-terminus sequence that is widely expressed in the brain. The shorter variant was reported to be irresponsive to hypoxia-a condition attributed to ischemia, which has put the neuroprotective role of hTREK-1 channel into question.
View Article and Find Full Text PDFStellate cells (SCs) of the medial entorhinal cortex (MEC) are rich in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are known to effectively shape their activity patterns. The explanatory mechanisms, however, have remained elusive. One important but previously unassessed possibility is that HCN channels control the gain of synaptic inputs to these cells.
View Article and Find Full Text PDFObjective: Much evidence suggests that the subiculum plays a significant role in the regulation of epileptic activity. Lactate acts as a neuroprotective agent against many conditions that cause brain damage. During epileptic seizures, lactate formation reaches up to ~6 mmol/L in the brain.
View Article and Find Full Text PDFWe present a waveguide integrated high-speed Si photodetector integrated with a silicon nitride (SiN) waveguide on an silicon-on-insulator (SOI) platform for short reach data communication in a 850 nm wavelength band. We demonstrate a waveguide couple Si pin photodetector responsivity of 0.44 A/W at 25 V bias.
View Article and Find Full Text PDFFast spiking interneurons (FSINs) have an important role in neuronal network dynamics. Although plasticity of synaptic properties is known to affect network synchrony, the role of plasticity of FSINs' intrinsic excitability on network dynamics remain elusive. Using computational approaches in an excitatory-FSIN model network (EI) based on previously established hippocampal neuronal models we show that altered FSIN intrinsic excitability robustly affects the coherence and frequency of network firing monotonically in the connected excitatory network.
View Article and Find Full Text PDFLearning in neuronal networks based on Hebbian principle has been shown to lead to destabilizing effects. Mechanisms have been identified that maintain homeostasis in such networks. However, the way in which these two opposing forces operate to support learning while maintaining stability is an active area of research.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
October 2018
TWIK-related potassium channel 1 (TREK1), a two-pore domain potassium channel, is modulated by various hormones and neurotransmitters by activation of membrane receptor - coupled second messengers. 17β-estradiol is a neuromodulator capable of regulating several cellular processes including the activity of ion channels, in a rapid and non-genomic manner. The G protein-coupled estrogen receptor (GPER) is known to facilitate rapid actions of 17β-estradiol, though its role in modulation of ion channels is not widely explored.
View Article and Find Full Text PDFConjunctive encoding of inputs has been hypothesized to be a key feature in the computational capabilities of the brain. This has been inferred based on behavioral studies and electrophysiological recording from animals. In this report, we show that random neuronal ensembles grown on multi-electrode array perform a coarse-conjunctive encoding for a sequence of inputs with the first input setting the context.
View Article and Find Full Text PDFPluripotent stem cells (PSCs) offer an excellent model to study neural development and function. Although various protocols have been developed to direct the differentiation of PSCs into desired neural cell types, many of them suffer from limitations including low efficiency, long duration of culture, and the use of expensive, labile, and undefined growth supplements. In this study, we achieved efficient differentiation of mouse PSCs to neural lineage, in the absence of exogenous molecules, by employing a serum-free culture medium containing knockout serum replacement (KSR).
View Article and Find Full Text PDFBrain ischaemia is a highly debilitating condition where shortage of oxygen and glucose leads to profuse cell death. Lactate is a neuroprotective metabolite whose concentrations increase up to 15-30 mmol/L during ischaemia and TREK1 is a neuroprotective potassium channel which is upregulated during ischaemia. The aim of this study was to investigate the effect of l-lactate on TREK1 expression and to evaluate the role of l-lactate-TREK1 interaction in conferring neuroprotection in ischaemia-prone hippocampus.
View Article and Find Full Text PDFTissue acidosis and high lactate concentrations are associated with cerebral ischaemia. The degree of acidosis is dependent on circulating glucose concentration, hyperglycaemia being associated with increased acidosis. Among other agents, lactate and protons have been shown to activate the leak potassium channel; TREK1 (TWIK related potassium channel 1) from the intracellular side and its increased activity is implicated in tolerance towards ischaemic cell damage.
View Article and Find Full Text PDFThe physiological metabolite, lactate and the two-pore domain leak potassium channel, TREK1 are known neuroprotectants against cerebral ischaemia. However, it is not known whether lactate interacts with TREK1 channel to provide neuroprotection. In this study we show that lactate increases TREK1 channel activity and hyperpolarizes CA1 stratum radiatum astrocytes in hippocampal slices.
View Article and Find Full Text PDFOxidative stress due to excessive accumulation of reactive oxygen or nitrogen species in the brain as seen in certain neurodegenerative diseases can have deleterious effects on neurons. Hydrogen peroxide, endogenously generated in neurons under normal physiological conditions, can produce an excess of hydroxyl radical via a Fenton mediated mechanism. This may induce acute oxidative injury if not scavenged or removed effectively by antioxidants.
View Article and Find Full Text PDFLithium is an effective mood stabilizer but its use is associated with many side effects. Electrophysiological recordings of miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate receptor AMPA-subtype (AMPARs) in hippocampal pyramidal neurons revealed that CLi (therapeutic concentration of 1 mM lithium, from days in vitro 4-10) decreased the mean amplitude and mean rectification index (RI) of AMPAR mEPSCs. Lowered mean RI indicate that contribution of Ca2+ -permeable AMPARs in synaptic events is higher in CLi neurons (supported by experiments sensitive to Ca2+ -permeable AMPAR modulation).
View Article and Find Full Text PDFThe structure of a new cysteine framework (-C-CC-C-C-C-) "M"-superfamily conotoxin, Mo3964, shows it to have a β-sandwich structure that is stabilized by inter-sheet cross disulfide bonds. Mo3964 decreases outward K(+) currents in rat dorsal root ganglion neurons and increases the reversal potential of the NaV1.2 channels.
View Article and Find Full Text PDFThe local fast-spiking interneurons (FSINs) are considered to be crucial for the generation, maintenance, and modulation of neuronal network oscillations especially in the gamma frequency band. Gamma frequency oscillations have been associated with different aspects of behavior. But the prolonged effects of gamma frequency synaptic activity on the FSINs remain elusive.
View Article and Find Full Text PDFLiquid State Machines have been proposed as a framework to explore the computational properties of neuro-electronic hybrid systems (Maass et al., 2002). Here the neuronal culture implements a recurrent network and is followed by an array of linear discriminants implemented using perceptrons in electronics/software.
View Article and Find Full Text PDFThe subiculum is a structure that forms a bridge between the hippocampus and the entorhinal cortex (EC), and plays a major role in the memory consolidation process. Here, we demonstrate spike-timing-dependent plasticity (STDP) at the proximal excitatory inputs on the subicular pyramidal neurons of juvenile rat. Causal (positive) pairing of a single EPSP with a single back-propagating action potential (bAP) after a time interval of 10 ms (+10 ms) failed to induce plasticity.
View Article and Find Full Text PDFThe subiculum, considered to be the output structure of the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, lateral septal region, thalamus, nucleus gelatinosus, medial nucleus and mammillary nuclei. Tonic inhibitory current plays an important role in neuronal physiology and pathophysiology by modulating the electrophysiological properties of neurons. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons expressing hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known.
View Article and Find Full Text PDFWhile the effect of stress on neuronal physiology is widely studied, its effect on the functionality of astrocytes is not well understood. We studied the effect of high doses of stress hormone corticosterone, on two physiological properties of astrocytes, i.e.
View Article and Find Full Text PDFHippocampal neurons are affected by chronic stress and have a high density of cytoplasmic mineralocorticoid and glucocorticoid receptors (MR and GR). Detailed studies on the genomic effects of the stress hormone corticosterone at physiologically relevant concentrations on different steps in synaptic transmission are limited. In this study, we tried to delineate how activation of MR and GR by different concentrations of corticosterone affects synaptic transmission at various levels.
View Article and Find Full Text PDFSynfire waves are propagating spike packets in synfire chains, which are feedforward chains embedded in random networks. Although synfire waves have proved to be effective quantification for network activity with clear relations to network structure, their utilities are largely limited to feedforward networks with low background activity. To overcome these shortcomings, we describe a novel generalisation of synfire waves, and define 'synconset wave' as a cascade of first spikes within a synchronisation event.
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