Memory in astrocytes: a hypothesis

BackgroundRecent work has indicated an increasingly complex role for astrocytes in the central nervous system. Astrocytes are now known to exchange information with neurons at synaptic junctions and to alter the information processing capabilities of the neurons. As an extension of this trend a hypothesis was proposed that astrocytes function to store information. To explore this idea the ion channels in biological membranes were compared to models known as cellular automata. These comparisons were made to test the hypothesis that ion channels in the membranes of astrocytes form a dynamic information storage device.ResultsTwo dimensional cellular automata were found to behave similarly to ion channels in a membrane when they function at the boundary between order and chaos. The length of time information is stored in this class of cellular automata is exponentially related to the number of units. Therefore the length of time biological ion channels store information was plotted versus the estimated number of ion channels in the tissue. This analysis indicates that there is an exponential relationship between memory and the number of ion channels. Extrapolation of this relationship to the estimated number of ion channels in the astrocytes of a human brain indicates that memory can be stored in this system for an entire life span. Interestingly, this information is not affixed to any physical structure, but is stored as an organization of the activity of the ion channels. Further analysis of two dimensional cellular automata also demonstrates that these systems have both associative and temporal memory capabilities.ConclusionIt is concluded that astrocytes may serve as a dynamic information sink for neurons. The memory in the astrocytes is stored by organizing the activity of ion channels and is not associated with a physical location such as a synapse. In order for this form of memory to be of significant duration it is necessary that the ion channels in the astrocyte syncytium be electrically in contact with each other. This function may be served by astrocyte gap junctions and suggests that agents that selectively block these gap junctions should disrupt memory.

[1]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[2]  J. Deleo,et al.  The Effect of Site and Type of Nerve Injury on Spinal Glial Activation and Neuropathic Pain Behavior , 1999, Experimental Neurology.

[3]  H. Komuro,et al.  Optical detection of postsynaptic potentials evoked by vagal stimulation in the early embryonic chick brain stem slice. , 1991, The Journal of physiology.

[4]  Y. Marunaka,et al.  Blocking action of cytochalasin D on protein kinase A stimulation of a stretch-activated cation channel in renal epithelial A6 cells. , 2001, Biochemical pharmacology.

[5]  H Machemer,et al.  Ionic conductances of membranes in ciliated and deciliated Paramecium. , 1979, The Journal of physiology.

[6]  R. Nicoll,et al.  Cyclic adenosine 3',5'‐monophosphate mediates beta‐receptor actions of noradrenaline in rat hippocampal pyramidal cells. , 1986, The Journal of physiology.

[7]  W. Hickey,et al.  Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat , 1997, Journal of Neuroimmunology.

[8]  N. Rickard,et al.  Complex Roles of Glutamate in the Gibbs—Ng Model of One-trial Aversive Learning in the New-born Chick , 1997, Neuroscience & Biobehavioral Reviews.

[9]  B. O'dowd,et al.  Astrocyte-Neuron Interaction During One-trial Aversive Learning in the Neonate Chick * * These results were originally presented at the Second Annual International Behavioral Neuroscience Society Conference, Clearwater Beach, Florida, USA, 22–25 April 1993. , 1996, Neuroscience & Biobehavioral Reviews.

[10]  L. Hertz,et al.  The effects of antidepressant drugs on adenylyl cyclase linked beta adrenergic binding sites on mouse astrocytes in primary cultures , 1983, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[11]  C. Giaume,et al.  Effects of General Anesthetics on Intercellular Communications Mediated by Gap Junctions between Astrocytes in Primary Culture , 1993, Anesthesiology.

[12]  J. Deitmer,et al.  Glial hyperpolarization upon nerve root stimulation in the leech Hirudo medicinalis , 1999, Glia.

[13]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[14]  David John Adams,et al.  Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons , 2001, Pflügers Archiv.

[15]  E. F. Codd,et al.  Cellular automata , 1968 .

[16]  L Cohen,et al.  Optical measurement of action potential activity in invertebrate ganglia. , 1989, Annual review of physiology.

[17]  H. Ogawa,et al.  Neuron-independent Ca2+ signaling in glial cells of snail’s brain , 2000, Neuroscience.

[18]  E. Richelson.  The use of cultured cells in the study of mood-normalizing drugs. , 1990, Pharmacology & toxicology.

[19]  M. Mynlieff.  Identification of different putative neuronal subtypes in cultures of the superior region of the hippocampus using electrophysiological parameters , 1999, Neuroscience.

[20]  B. Cooper,et al.  Subclassified acutely dissociated cells of rat DRG: histochemistry and patterns of capsaicin-, proton-, and ATP-activated currents. , 2000, Journal of neurophysiology.

[21]  James M. Robertson.  The Astrocentric Hypothesis: proposed role of astrocytes in consciousness and memory formation , 2002, Journal of Physiology-Paris.

[22]  Adrian Y. C. Wong,et al.  Single channel properties of P2X ATP receptors in outside‐out patches from rat hippocampal granule cells , 2000, The Journal of physiology.

[23]  T. Sibaoka.  Action potentials in plant organs. , 1966, Symposia of the Society for Experimental Biology.

[24]  S. Chiu,et al.  Neurotransmitter‐mediated signaling between axons and glial cells , 1994, Glia.

[25]  Stephen Wolfram,et al.  Universality and complexity in cellular automata , 1983 .

[26]  H. Chiang,et al.  Vinpocetine-induced stimulation of calcium-activated potassium currents in rat pituitary GH3 cells. , 2001, Biochemical pharmacology.

[27]  Franco Bagnoli,et al.  Cellular Automata , 2002, Lecture Notes in Computer Science.

[28]  R. Caudle.  The demonstration of long latency potentials in the CA1 region of the rat hippocampal slice , 1993, Brain Research.

[29]  B Bioulac,et al.  Activation of GABA(A) receptors in subthalamic neurons in vitro: properties of native receptors and inhibition mechanisms. , 2001, Journal of neurophysiology.

[30]  A. Rodríguez-Contreras,et al.  Direct measurement of single‐channel Ca2+ currents in bullfrog hair cells reveals two distinct channel subtypes , 2001, The Journal of physiology.

[31]  C. Triggle,et al.  State-dependent block of rabbit vascular smooth muscle delayed rectifier and Kv1.5 channels by inhibitors of cytochrome P450-dependent enzymes. , 2001, The Journal of pharmacology and experimental therapeutics.

[32]  M. Pellegrino,et al.  Stretch‐activated cation channels of leech neurons exhibit two activity modes , 2001, The European journal of neuroscience.

[33]  C. Rose,et al.  Gap junctions equalize intracellular Na+ concentration in astrocytes , 1997, Glia.

[34]  Giorgio Carmignoto,et al.  Calcium oscillations encoding neuron-to-astrocyte communication , 2002, Journal of Physiology-Paris.

[35]  H. Hydén,et al.  Nuclear RNA changes of nerve cells during a learning experiment in rats. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[36]  S. Maier,et al.  Spinal gap junctions: potential involvement in pain facilitation. , 2004, The journal of pain : official journal of the American Pain Society.

[37]  T. Moser.  Low‐conductance intercellular coupling between mouse chromaffin cells in situ , 1998, The Journal of physiology.

[38]  A. Araque,et al.  Dynamic signaling between astrocytes and neurons. , 2001, Annual review of physiology.

[39]  J. P. Huston,et al.  Stimulus complexity dependent memory impairment and changes in motor performance after deletion of the neuronal gap junction protein connexin36 in mice , 2005, Behavioural Brain Research.

[40]  E. Hansson,et al.  Signaling and gene expression in the neuron–glia unit during brain function and dysfunction: Holger Hydén in memoriam , 2001, Neurochemistry International.

[41]  F. Attneave,et al.  The Organization of Behavior: A Neuropsychological Theory , 1949 .

[42]  Giorgio Carmignoto,et al.  Reciprocal communication systems between astrocytes and neurones , 2000, Progress in Neurobiology.

[43]  Yu-liang Shi,et al.  Modulation of inward rectifier potassium channel by toosendanin, a presynaptic blocker , 2001, Neuroscience Research.

[44]  C. Naus,et al.  General anesthetics attenuate gap junction coupling in P19 cell line , 2005, Journal of neuroscience research.

[45]  K. Willecke,et al.  Connexin30‐deficient mice show increased emotionality and decreased rearing activity in the open‐field along with neurochemical changes , 2003, The European journal of neuroscience.

[46]  L. Cohen,et al.  Nonuniform expression of habituation in the activity of distinct classes of neurons in the Aplysia abdominal ganglion , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  L. Hertz,et al.  Acute and chronic effects of antidepressant drugs on β‐adrenergic function in astrocytes in primary cultures: An indication of glial involvement in affective disorders? , 1983, Journal of neuroscience research.

[48]  A. Harper,et al.  Characterization of the large-conductance Ca-activated K channel in myocytes of rat saphenous artery , 2000, Pflügers Archiv.

[49]  G. Perea,et al.  Properties of Synaptically Evoked Astrocyte Calcium Signal Reveal Synaptic Information Processing by Astrocytes , 2005, The Journal of Neuroscience.

[50]  Uwe Freiwald,et al.  The Java based cellular automata simulation system--JCASim , 2002, Future Gener. Comput. Syst..

[51]  W G Wier,et al.  Rapid communication between neurons and astrocytes in primary cortical cultures , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  D. Schiminovich,et al.  Distributed aspects of the response to siphon touch in Aplysia: spread of stimulus information and cross-correlation analysis , 1994, Journal of Neuroscience.

[53]  Eduardo D. Martín,et al.  Synaptically Released Acetylcholine Evokes Ca2+Elevations in Astrocytes in Hippocampal Slices , 2002, The Journal of Neuroscience.

[54]  John von Neumann,et al.  Theory Of Self Reproducing Automata , 1967 .

[55]  B. Renouf,et al.  MAP kinase activation by fluoxetine and its relation to gene expression in cultured rat astrocytes , 2007, Journal of Molecular Neuroscience.

[56]  Christopher G. Langton,et al.  Computation at the edge of chaos: Phase transitions and emergent computation , 1990 .

[57]  H. Hydén,et al.  GLIAL RNA CHANGES DURING A LEARNING EXPERIMENT IN RATS. , 1963, Proceedings of the National Academy of Sciences of the United States of America.

[58]  M. Aminoff.  Principles of Neural Science. 4th edition , 2001 .

[59]  L. Hertz,et al.  Diazepam receptors on mouse astrocytes in primary cultures: displacement by pharmacologically active concentrations of benzodiazepines or barbiturates. , 1980, Canadian journal of physiology and pharmacology.

[60]  D. Kleinfeld,et al.  Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices. , 1997, Cerebral cortex.

[61]  C. Gibbs,et al.  Ion involvement in memory formation: the potential role of astrocytes. , 1992, Progress in brain research.

[62]  E. Carbone,et al.  Direct autocrine inhibition and cAMP‐dependent potentiation of single L‐type Ca2+ channels in bovine chromaffin cells , 2001, The Journal of physiology.

[63]  J. Han,et al.  Trifluoroacetic acid activates ATP-sensitive K(+) channels in rabbit ventricular myocytes. , 2001, Biochemical and biophysical research communications.

[64]  E. Dere,et al.  Mice with astrocyte‐directed inactivation of connexin43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels , 2003, The European journal of neuroscience.

[65]  T. Hwang,et al.  Voltage‐dependent flickery block of an open cystic fibrosis transmembrane conductance regulator (CFTR) channel pore , 2001, The Journal of physiology.

[66]  J. Tillement,et al.  Desipramine treatment differently down-regulates beta-adrenoceptors of freshly isolated neurons and astrocytes. , 1996, European journal of pharmacology.

[67]  E. Barrett,et al.  Separation of two voltage‐sensitive potassium currents, and demonstration of a tetrodotoxin‐resistant calcium current in frog motoneurones. , 1976, The Journal of physiology.

[68]  Astrocyte-neurone crosstalk: variants of the same language? , 2000, Trends in pharmacological sciences.

[69]  W. Kristan,et al.  Glial responses during evoked behaviors in the leech , 1999, Glia.

[70]  Moshe Sipper,et al.  Toward a viable, self-reproducing universal computer , 1996 .