NMDA receptors as voltage sensors

© Springer Science+Business Media LLC 2017. The membrane potential is an essential parameter of a living cell. However, measurements of the membrane potential using conventional techniques are associated with a number of artifacts. Cell-attached recordings of the currents through NMDA receptor channels enable noninvasive measurements of the neuronal membrane potential. This approach overcomes the problem of a leak conductance introduced during intracellular sharp electrode recordings and whole-cell patch-clamp recordings. Here, we describe the procedures of using cell-attached recordings of NMDA receptor channels to measure the true membrane potential

Dynamics of the Hypoxia—Induced Tissue Edema in the Rat Barrel Cortex in vitro

Cerebral edema is a major, life threatening complication of ischemic brain damage. Previous studies using brain slices have revealed that cellular swelling and a concomitant increase in tissue transparency starts within minutes of the onset of metabolic insult in association with collective anoxic spreading depolarization (aSD). However, the dynamics of tissue swelling in brain slices under ischemia-like conditions remain elusive. Here, we explored the dynamics of brain tissue swelling induced by oxygen-glucose deprivation (OGD) in submerged rat barrel cortex slices. Video monitoring of the vertical and horizontal position of fluorescent dye-filled neurons and contrast slice surface imaging revealed elevation of the slice surface and a horizontal displacement of the cortical tissue during OGD. The OGD-induced tissue movement was also associated with an expansion of the slice borders. Tissue swelling started several minutes after aSD and continued during reperfusion with normal solution. Thirty minutes after aSD, slice borders had expanded by ~130 μm and the slice surface had moved up to attain a height of ~70 μm above control levels, which corresponded to a volume increase of ~30%. Hyperosmotic sucrose solution partially reduced the OGD-induced slice swelling. Thus, OGD-induced cortical slice tissue swelling in brain slices in vitro recapitulates many features of ischemic cerebral edema in vivo, its onset is tightly linked to aSD and it develops at a relatively slow pace after aSD. We propose that this model of cerebral edema in vitro could be useful for the exploration of the pathophysiological mechanisms underlying ischemic cerebral edema and in the search for an efficient treatment to this devastating condition

Bilateral Synchronization of Hippocampal Early Sharp Waves in Neonatal Rats

In the neonatal rodent hippocampus, the first and predominant pattern of correlated neuronal network activity is early sharp waves (eSPWs). Whether and how eSPWs are organized bilaterally remains unknown. Here, using simultaneous silicone probe recordings from the left and right hippocampus in neonatal rats in vivo we found that eSPWs are highly synchronized bilaterally with nearly zero time lag between the two sides. The amplitudes of eSPWs in the left and right hippocampi were also highly correlated. eSPWs also supported bilateral synchronization of multiple unit activity (MUA). We suggest that bilateral correlated activity supported by synchronized eSPWs participates in the formation of bilateral connections in the hippocampal system

How Relations are Built within a SNS World: Social Network Analysis on Mixi

Our purpose here is to (1) investigate the structure of the personal networks developed on mixi, a Japanese social networking service (SNS), and (2) to consider the governing mechanism which guides participants of a SNS to form an aggregate network. Our findings are as follows:the clustering coefficient of the network is as high as 0.33 while the characteristic path lenght is as low as 5.5. A network among central users (over 300 edges) consist of two cliques, which seems to be very fragile. Community-affiliation network suggests there are several easy-entry communities which later lead users to more high-entry, unique-theme communities. The analysis on connectedness within a community reveals the importance of real-world interaction. Lastly, we depict a probable image of the entire ecology on mixi among users and communities, which contributes broadly to social systems on the Web

Ontogeny of kainate-induced gamma oscillations in the rat CA3 hippocampus in vitro

International audienceGABAergic inhibition, which is instrumental in the generation of hippocampal gamma oscillations, undergoes significant changes during development. However, the development of hippocampal gamma oscillations remains largely unknown. Here, we explored the developmental features of kainate-induced oscillations (KA-Os) in CA3 region of rat hippocampal slices. Up to postnatal day P5, the bath application of kainate failed to evoke any detectable oscillations. KA-Os emerged by the end of the first postnatal week; these were initially weak, slow (20-25 Hz, beta range) and were poorly synchronized with CA3 units and synaptic currents. Local field potential (LFP) power, synchronization of units and frequency of KA-Os increased during the second postnatal week to attain gamma (30-40 Hz) frequency by P15-21. Both beta and gamma KA-Os are characterized by alternating sinks and sources in the pyramidal cell layer, likely generated by summation of the action potential associated currents and GABAergic synaptic currents, respectively. Blockade of GABA(A) receptors with gabazine completely suppressed KA-Os at all ages indicating that GABAergic mechanisms are instrumental in their generation. Bumetanide, a NKCC1 chloride co-transporter antagonist which renders GABAergic responses inhibitory in the immature hippocampal neurons, failed to induce KA-Os at P2-4 indicating that the absence of KA-Os in neonates is not due to depolarizing actions of GABA. The linear developmental profile, electrographic features and pharmacological properties indicate that CA3 hippocampal beta and gamma KA-Os are fundamentally similar in their generative mechanisms and their delayed onset and developmental changes likely reflect the development of perisomatic GABAergic inhibition

Early patterns of activity in the developing cortex: Focus on the sensorimotor system

© 2017 Elsevier Ltd. Early development of somatotopic cortical maps occurs during the fetal period in humans and during the postnatal period in rodents. During this period, the sensorimotor cortex expresses transient patterns of correlated neuronal activity including delta waves, gamma- and spindle-burst oscillations. These early activity patterns are largely driven by the thalamus and triggered, in a topographic manner, by sensory feedback resulting from spontaneous movements. Early cortical activities are instrumental for competitive interactions between sensory inputs for the cortical territories, they prevent cortical neurons from apoptosis and their alteration may lead to disturbances in cortical network development in a number of neurodevelopmental diseases

Spontaneous activity in developing sensory circuits: Implications for resting state fMRI

The immature brain spontaneously expresses unique patterns of electrical activity that are believed to contribute to the development of neuronal networks. Certain electrographic features of this activity, particularly modulation on an infraslow time scale, resemble activity patterns observed in the mature brain at 'rest', loosely defined as the absence of an investigator imposed task. However, it is not clear whether the immature activity patterns observed at rest are precursors of the spontaneous neuronal activity that forms resting state networks in the adult. Here, we review recent studies that have explored the generative mechanisms of resting state activity during development in the primary sensory systems of premature human neonates and neonatal rodents. The remarkable hypothesis suggested by this work is that while resting state activity during the pre- and possibly near-term period can bear superficial resemblance to adult activity it is fundamentally different in terms of function and origin. During early development spontaneous thalamocortical activity in primary sensory regions is determined largely by transitory generators in the sensory periphery. This is in contrast to the adult, where spontaneous activity generated within thalamocortex, particularly by cortico-cortical connections, dominates. We therefore suggest a conservative interpretation of developmental mapping studies which are based on indirect measurement of activity (e.g. fMRI), or on the partitioning of EEG frequency using bands derived from adult studies. The generative mechanisms for brain activity at early ages are likely different from those of adults, and may play very different roles; for example in circuit formation as opposed to attention. © 2012 Elsevier Inc

Rapid cortical oscillations and early motor activity in premature human neonate.

International audienceDelta-brush is the dominant pattern of rapid oscillatory activity (8-25 Hz) in the human cortex during the third trimester of gestation. Here, we studied the relationship between delta-brushes in the somatosensory cortex and spontaneous movements of premature human neonates of 29-31 weeks postconceptional age using a combination of scalp electroencephalography and monitoring of motor activity. We found that sporadic hand and foot movements heralded the appearance of delta-brushes in the corresponding areas of the cortex (lateral and medial regions of the contralateral central cortex, respectively). Direct hand and foot stimulation also reliably evoked delta-brushes in the same areas. These results suggest that sensory feedback from spontaneous fetal movements triggers delta-brush oscillations in the central cortex in a somatotopic manner. We propose that in the human fetus in utero, before the brain starts to receive elaborated sensory input from the external world, spontaneous fetal movements provide sensory stimulation and drive delta-brush oscillations in the developing somatosensory cortex contributing to the formation of cortical body maps

Temporal Coding at the Immature Depolarizing GABAergic Synapse

In the developing hippocampus, GABA exerts depolarizing and excitatory actions and contributes to the generation of neuronal network driven giant depolarizing potentials (GDPs). Here, we studied spike time coding at immature GABAergic synapses and its impact on synchronization of the neuronal network during GDPs in the neonatal (postnatal days P2–6) rat hippocampal slices. Using extracellular recordings, we found that the delays of action potentials (APs) evoked by synaptic activation of GABA(A) receptors are long (mean, 65 ms) and variable (within a time window of 10–200 ms). During patch-clamp recordings, depolarizing GABAergic responses were mainly subthreshold and their amplification by persistent sodium conductance was required to trigger APs. AP delays at GABAergic synapses shortened and their variability reduced with an increase in intracellular chloride concentration during whole-cell recordings. Negative shift of the GABA reversal potential (EGABA) with low concentrations of bumetanide, or potentiation of GABA(A) receptors with diazepam reduced GDPs amplitude, desynchronized neuronal firing during GDPs and slowed down GDPs propagation. Partial blockade of GABA(A) receptors with bicuculline increased neuronal synchronization and accelerated GDPs propagation. We propose that spike timing at depolarizing GABA synapses is determined by intracellular chloride concentration. At physiological levels of intracellular chloride GABAergic depolarization does not reach the action potential threshold and amplification of GABAergic responses by non-inactivating sodium conductance is required for postsynaptic AP initiation. Slow and variable excitation at GABAergic synapse determines the level of neuronal synchrony and the rate of GDPs propagation in the developing hippocampus

Depolarizing GABA and developmental epilepsies

© 2014 John Wiley & Sons Ltd. Early in development, GABA, which is the main inhibitory neurotransmitter in adult brain, depolarizes immature neurons and exerts dual-excitatory and shunting/inhibitory-effects in the developing neuronal networks. The present review discusses some general questions, including the properties of excitation at depolarizing GABAergic synapse and shunting inhibition by depolarizing GABA; technical issues in exploration of depolarizing GABA using various techniques and preparations, including the developmental aspects of traumatic injury and what is known (or rather unknown) on the actions of GABA in vivo; complex roles of depolarizing GABA in developmental epilepsies, including a contribution of depolarizing GABA to enhanced excitability in the immature networks, caused by repetitive seizures accumulation of intracellular chloride concentration that increases excitatory GABA power and its synchronizing proconvulsive effects, and correction of chloride homeostasis as a potential strategy to treat neonatal seizures