Cells are not solitary individuals. They function in an orchestra, a syncytium. They are social and talk to each other. They can sing, and they can scream or make noise, be rebellious. And I have always thought that the song is the good one, that which organize and regulate the cells. That the noise is the bad guy, that brings pain and sickness. Then I read that the noise is the regulating one. In biology, nothing is what it used to be any more. The world has turned upside down. And we must try to extract the truth from that resulting mess.
That the noise is the regulating force, or the basic information, is true for the nerve pulse in the solitone. Also in the brainstem the RAS-network inhibite strongly the impulses from the body, and a further inhibition is done by the blood-brain barrier (tight junction) and modulation by neurotransmitters and peptides. Modulation change the brainwaves and gives them a higher amplitude. Most of the modulation is done in the midbrain in thalamus-hypothalamus region as emotions. Cortical modulation is done by neurotransmitters. The "driving force" is glutamat, and inhibitory force is GABA.
Said in another way - the synchrony is high when the impulse rate is low, see fig. and an animation here. Electrical synapses stabilizes the synchronization. cit. "The oscillations with small amplitudes near the origin corresponded to stochastic synchrony where the ensembleaveraged dynamics shows synchronization in the network but each neuron has a low firing rate and the firing seems to be stochastic. We found stochastic synchrony that corresponded to a chaotic attractor, and we called this phenomenon stochastic synchrony of chaos."
Stochastic synchrony is a phenomenon where the ensemble-averaged dynamics of the network shows synchronization, but the firing rate of each neuron is very low (weak synchronization).
In stochastic synchrony of chaos, the ensemble-averaged dynamics is chaotic. A typical firing pattern of stochastic synchrony of chaos is shown, see Fig. Inhibitory neurons and electrical synapses are important (1).
When stochastic synchrony exists in a network, the contribution of a single neuron in the network to the synchronization is small. Therefore, this neuron might also contribute to form other synchronous networks simultaneously. We get dynamical cell assemblies, reentrant loops in brain a la Edelman, or multichannel neurons. "The question of how a nerve communicates remains unanswered. It is a huge, gaping hole, at the most basic level, in our understanding of how the nervous system works" asks the author.
The dendritic loop/tripartite synapse
There are four types of connections among excitatory and inhibitory assemblies. Are these corresponding to the different brainwave levels? For ex. when visual stimulation was given to cats, oscillations of 40 Hz appeared in the local field potential in the visual cortex and when correlated inputs were given to the receptive fields of each assembly, synchronization among distant (c.7mm) assemblies appeared.
There are also self-oscillating neurons. Autonomous firing.
The modern view holds the neuron as a discrete cell that processes information in more ways than originally envisaged. Intercellular communication by gap junctions, slow electrical potentials, action potentials initiated in dendrites, neuromodulatory effects, extrasynaptic release of neurotransmitters, and information flow between neurons and glia all contribute to information processing. The tripartite synapse is very important.
Dendrites are the analog part of the neurone, and the action potentials are built up in the dendritic tree as an intracellular Ca-wave in form of second messenger.
Collective ion channel gating
Receptor cells make up a syncytium. The response property of the receptor cells, or syncytia, depends on dynamics of collective ion channel gating in the cells, which are 1. periodic, 2. stably chaotic, and 3. unstably chaotic. The dynamics of unstable chaos state synchronizes the potential variation of all receptor cells in the syncytium induced by external stimuli. The syncytium system in the stable and unstable chaos states can detect a weak periodic input signal without assistance of any level of noise (2).
Impulse strength regulation
Then I read that in learning there are rapid shifts of AMPA and NMDA receptors due to exo- and endocytosis, that is communication with the intercellular environment. LTD (and LTP?) is at least partly postsynaptic, and a functional consequence of dendritic protein synthesis is the regulation of glutamate receptor trafficking (3).
Application of amyloid-beta (Alzheimers) promoted endocytosis of NMDA receptors in cortical neurons (4). In addition, neurons from a genetic mouse model of Alzheimer disease expressed reduced amounts of surface NMDA receptors. Reducing amyloid-beta by treating neurons with a gamma-secretase inhibitor restored surface expression of NMDA receptors. Phosphorylation and dephosphorylation seem to be very important, and with it the flux of receptors on/off and the information trafficing. And outside the cell there must be a pool of receptors in off-stage. Also the cytoskeleton is very important, so Ca and Mg (5). The degree of activity of NMDARs is determined in part by extracellular Mg(2+) and by the co-agonists for this receptor, glycine and D-serine (note trans-form). During strong stimulation, a relief of the voltage-dependent block of NMDARs by Mg(2+) provides a positive feedback (5). Alterations in the various balances underlie "meta-plasticity."
So chaos sends the message which the more harmonious states (= slow) detect? In the nerve pulse the solitone is scanning the fibre for disturbances = inputs of information to the system. The harmonious states are the ground states? What makes the information detectable?
Epilepsy shows glutamate synchronize too
Glia and astrocytes make up most of the cells in the brain. It is now becoming clear that these cells make crucial contributions to the formation, operation and adaptation of neural circuitry. The synchrony of abnormally excitable neurons, or even hypersynchrony, is a hallmark in epileptic seizure. Neurons in the brain of individuals with focal epilepsy exhibit sustained discharges, called paroxysmal depolarization shifts. Epileptic discharges are in part initiated by a local depolarization shift that drives groups of neurons into synchronous bursting(11). Unexpected new evidence indicates that glutamate release from glia can generate these events, and may serve to synchronize the activity of neurons (10). Shifts can also be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca2+ in astrocytes. Too big Ca2+-waves are responsible? The mechanisms underlying simultaneous activation of multiple neurons remains still unclear. For epilepsy the astrocytes are very interesting medical targets.
The nonlinear oscillations in two neurons coupled via gap junction in epilepsy, the model of a pair of neurons is derived from Chay model that gives many kinds of abnormal oscillations in excitable neurons by three nonlinear variables dynamics equations. The synchrony between two electrically coupled excitable neurons is found and a theoretical effort is carried out to investigate the chaos in the synchronous oscillations of the membrane potentials by the Lyapunov exponent and the phase portrait. It is shown that synchronous abnormal oscillations of membrane potentials can occur when the coupling strength of gap junction is large enough and the concentration of Ca2 ions does not synchronize while the membrane potentials are synchronous and the coupling mechanism is chaotic (6). It is concluded that the synchrony and the chaos make birth to the new oscillations while disorder process such as epileptic seizure.
A schematic representation of the current and fluxes captured by the Chay 1997 pancreatic beta-cell model. This diagram shows the plasma membrane currents associated with burst and spike oscillations: the fast current, Ifast; the calcium current, I Ca2+ ; the cationic nonselective inward current, INS; the delayed-rectifying K+ current, IK(dr), the calcium-sensitive K+ current, IK(Ca); the ATP-sensitive K+ current, IK(ATP); and the Na+ leak current, INa(L). The ER intracellular Ca2+ store is also shown with its associated transmembrane calcium fluxes: calcium release, Jrel; and calcium uptake by the Ca2+-ATPase, Jpump (7).
Inhibition of impulse
GABA A and GABA B Synapses Play Opposite Roles in Synchronization. They are inhibitory signals(9). Asynchronous release can be seen as a way to produce long-lasting inhibition despite the fast decay time of individual events mediated by GABA A receptors. Asynchronous GABA release produces long-lasting inhibition and accentuates temporal dispersion. Network heterogeneity and synaptic failure play the same role in breaking synchrony.
Schwann cells are the glial cells of the peripheral nervous system. They form myelin sheaths, which are essential for saltatory conduction in normal nerves, and promote axonal regeneration in damaged nerves. The transcription factor NF- B, increasingly recognized as a key regulator of developmental and adult neural plasticity, is now reported to be essential for axon myelination as well. What about its function. An isolator, and what more?
Chaos in synchrony of abnormal oscillations
The neurons are connected by both chemical synapses and electrical synapses among the inhibitory neurons. The synchronous firing of neurons in a pulse-coupled neural network composed of excitatory and inhibitory neurons shows that when electrical synapses are introduced, periodically synchronized firing as well as chaotically synchronized firing is widely observed. Moreover, we find stochastic synchrony where the ensemble-averaged dynamics shows synchronization in the network but each neuron has a low firing rate and the firing of the neurons seems to be stochastic. Stochastic synchrony of chaos corresponding to a chaotic attractor is also found (1).
Gamma-frequency (30-70 Hz) oscillations in populations of interneurons may induce synchronous firing in principal neuron networks. Such a role would require that neurons, 1 mm or more apart, are able to synchronize their activity, despite the presence of axonal conduction delays and of the limited axonal spread of many interneurons. Interneuron doublet firing can help to synchronize gamma oscillations, provided that sufficiently many pyramidal neurons are active; gap junctions, between the axons of principal neurons, could contribute to the long-range synchrony of gamma oscillations (in vitro). (Gamma oscillations in isolated networks of tonically excited interneurons, with frequency gated by mutual GABA(A) receptor-mediated IPSPs (interneuron network gamma)). There is simulation and electrophysiological evidence that interneuronal gap junctions (presumably dendritic) can enhance the synchrony of such gamma oscillations (7), in spatially extended interneuron networks. There appears to be a sharp threshold conductance, below which the interneuron dendritic gap junctions do not exert a synchronizing role.
The astroglial syncytium
Glial cells is part of the connective tissue, that made up one single sheat of cells going through the whole body. The sheat has "pockets" for the organs, and fascias make up the "high roads". And there are a lot of fast connections between the cells. Small aqueous pores, the gap junction channels, couple glial astrocytes into an extensive syncytium-like organisation. Astrocytes are the most abundant cell type in the central nervous system (CNS) and increasing evidence now suggests that they play an active role in various brain functions. Astrocytes are involved in the induction and maintenance of the blood brain barrier, as well as the induction and stabilization of neuronal synapses (8).
Astroglial gap junctions are mainly composed of connexin-43 proteins. They provide a pathway for intercellular diffusion of ions and small ((1000 Da) molecules, such as second messengers as Ca2+ and metabolites. Moreover, astrocytes control the extracellular ionic homeostasis, recycle neurotransmitters and painsgiving substance P among others.
Astrocytes become reactive, a process known as reactive gliosis, in CNS pathologies, such as ischemia, neurotrauma or neurodegeneration. Reactive astrocytes seem to be protective at an early stage after neurotrauma but inhibit regeneration later on.
The organisation into multicellular functional units is probably a prerequisite for the participation of astroglial cells in the control of extracellular homeostasis. Waves of increased intracellular Ca2+ concentration can propagate between astrocytes. This is of particular interest, as cytosolic Ca2+ is a second messenger that affects ion channels, carriers, and enzymes and thereby mediates short-, intermediate-, and long-term effects on astroglial function. The modulation of gap junction communication and intra- and intercellular Ca2+ signalling induced by various neuroactive substances may depend on differences in connexin-43 expression, gap junction communication, and Ca2+ signalling in various brain regions.
1. Takashi Kanamaru and Kazuyuki Aihara 2008: Stochastic synchrony of chaos in a pulse coupled neural network with both chemical and electrical synapses among inhibitory neurons, Neural Computation, vol.20, no.8 (2008) pp.1951-1972. http://brain.cc.kogakuin.ac.jp/~kanamaru/Chaos/e/sSync/kanamaru-nc2008.pdf
2. Funakubo, H. Kashimori, Y. Kambara, T. 1997: Stable and unstable chaos states of receptor cell syncytium and stochastic resonance without noise. Neural Networks,1997. International Conference on... Publication Date: 9-12 Jun 1997: vol.1: 318-323. http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?tp=&arnumber=611686&isnumber=13361
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4. Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P. 2005: Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci. 2005 Aug;8(8):1051-8. http://www.ncbi.nlm.nih.gov/pubmed/16025111?ordinalpos=38&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum">endocytosis
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6. Ge Manling Guo Hongyong Dong Guoya Jia Wenyan Li Ying Sun Minggui Wang Baozhu Yan Weili 2004: The chaos in the synchrony of abnormal oscillations in a pair of neurons coupled via gap junction. Signal Processing, 2004. Proceedings. ICSP '04. 2004 7th International Conference on...vol.3: 2210- 2213 ISBN: 0-7803-8406-7 http://ieeexplore.ieee.org/Xplore/login.jsp?url=http%3A%2F%2Fieeexplore.ieee.org%2Fiel5%2F9834%2F30995%2F01442217.pdf&authDecision=-203
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8. Nicola J. Allen & Ben A. Barres 2009: Neuroscience: Glia — more than just brain glue. Nature 457, 675-677. http://www.nature.com/nature/journal/v457/n7230/full/457675a.html
9. Martinez D, Montejo N, 2008 A Model of Stimulus-Specific Neural Assemblies in the Insect Antennal Lobe. PLoS Comput Biol 4(8): e1000139. doi:10.1371/journal.pcbi.1000139 http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000139
10. Michael A Rogawski(2005): Astrocytes get in the act in epilepsy. Nature Medicine 11, 919 - 920. http://www.nature.com/nm/journal/v11/n9/abs/nm0905-919.html
11.Guo-Feng Tian et.al. (2005): An astrocytic basis of epilepsy. Nature Medicine 11, 973 - 981. http://www.nature.com/nm/journal/v11/n9/abs/nm1277.html