The dynamics of free calcium in dendritic spines in response to repetitive synaptic input.

Increased levels of intracellular calcium at either pre- or postsynaptic sites are thought to precede changes in synaptic strength. Thus, to induce long-term potentiation in the hippocampus, periods of intense synaptic stimulation would have to transiently raise the levels of cytosolic calcium at postsynaptic sites--dendritic spines in the majority of cases. Since direct experimental verification of this hypothesis is not possible at present, calcium levels have been studied by numerically solving the appropriate electro-diffusion equations for two different postsynaptic structures. Under the assumption that voltage-dependent calcium channels are present on dendritic spines, free intracellular calcium in spines can reach micromolar levels after as few as seven spikes in 20 milliseconds. Moreover, a short, but high-frequency, burst of presynaptic activity is more effective in raising levels of calcium and especially of the calcium-calmodulin complex than sustained low-frequency activity. This behavior is different from that seen at the soma of a typical vertebrate neuron.

[1]  T. Blackstad,et al.  An electron microscopic study of the stratum radiatum of the rat hippocampus (regio superior, CA 1) with particular emphasis on synaptology , 1962, The Journal of comparative neurology.

[2]  S. Jacobson Dimensions of the dendritic spine in the sensorimotor cortex of the rat, cat, squirrel monkey and man , 1967 .

[3]  J. Scholey,et al.  Regulation of non-muscle myosin assembly by calmodulin-dependent light chain kinase , 1980, Nature.

[4]  J. Wood,et al.  Immunocytochemical localization of calmodulin and a heat-labile calmodulin-binding protein (CaM-BP80) in basal ganglia of mouse brain , 1980, The Journal of cell biology.

[5]  E. Kandel Calcium and the control of synaptic strength by learning , 1981, Nature.

[6]  Paul R. Adams,et al.  Voltage-clamp analysis of muscarinic excitation in hippocampal neurons , 1982, Brain Research.

[7]  F. Crick Do dendritic spines twitch? , 1982, Trends in Neurosciences.

[8]  J. Miller,et al.  Calcium-induced long-term potentiation in the hippocampus , 1982, Neuroscience.

[9]  G. Lynch,et al.  Intracellular injections of EGTA block induction of hippocampal long-term potentiation , 1983, Nature.

[10]  T. H. Brown,et al.  Associative long-term potentiation in hippocampal slices. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Eccles Calcium in long-term potentiation as a model for memory , 1983, Neuroscience.

[12]  F. F. Weight,et al.  Detection of intracellular Ca2+ transients in sympathetic neurones using arsenazo III , 1983, Nature.

[13]  T. Poggio,et al.  A theoretical analysis of electrical properties of spines , 1983, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[14]  J. A. Markham,et al.  Calcium in the spine apparatus of dendritic spines in the dentate molecular layer , 1983, Brain Research.

[15]  R. Dipolo,et al.  The calcium pump and sodium-calcium exchange in squid axons. , 1983, Annual review of physiology.

[16]  H. Rasmussen,et al.  Calcium messenger system: an integrated view. , 1984, Physiological reviews.

[17]  F. Crick Neurobiology: Memory and molecular turnover , 1984, Nature.

[18]  D. Alkon Calcium-mediated reduction of ionic currents: a biophysical memory trace. , 1984, Science.

[19]  G. Lynch,et al.  The biochemistry of memory: a new and specific hypothesis. , 1984, Science.

[20]  D. Alkon,et al.  Ca2+-dependent protein kinase injection in a photoreceptor mimics biophysical effects of associative learning. , 1984, Science.

[21]  J. Lisman A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[22]  D L Alkon,et al.  Calcium activates and inactivates a photoreceptor soma potassium current. , 1985, Biophysical journal.

[23]  Idan Segev,et al.  Signal enhancement in distal cortical dendrites by means of interactions between active dendritic spines. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[24]  F. Pongrácz,et al.  The function of dendritic spines: A theoretical study , 1985, Neuroscience.

[25]  D H Perkel,et al.  The function of dendritic spines: a review of theoretical issues. , 1985, Behavioral and neural biology.

[26]  J. Miller,et al.  Synaptic amplification by active membrane in dendritic spines , 1985, Brain Research.

[27]  Stephen J. Smith,et al.  NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones , 1986, Nature.

[28]  D. Alkon,et al.  Modulation of calcium-mediated inactivation of ionic currents by Ca2+/calmodulin-dependent protein kinase II. , 1986, Biophysical journal.

[29]  H. Wigström,et al.  Hippocampal long-term potentiation is induced by pairing single afferent volleys with intracellularly injected depolarizing current pulses. , 1986, Acta physiologica Scandinavica.

[30]  S. Kelso,et al.  Hebbian synapses in hippocampus. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[31]  C. Cotman,et al.  Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl d-aspartate antagonists , 1986, Neuroscience Letters.

[32]  P. Adams,et al.  Voltage-dependent currents of vertebrate neurons and their role in membrane excitability. , 1986, Advances in neurology.

[33]  K. Krnjević,et al.  Changes in free calcium ion concentration recorded inside hippocampal pyramidal cells in situ , 1986, Brain Research.

[34]  C Koch,et al.  Slow synaptic transmission in frog sympathetic ganglia. , 1986, The Journal of experimental biology.

[35]  J. Winson,et al.  Long-term potentiation in dentate gyrus: induction by asynchronous volleys in separate afferents. , 1986, Science.

[36]  R. Malinow,et al.  Postsynaptic hyperpolarization during conditioning reversibly blocks induction of long-term potentiation , 1986, Nature.

[37]  M. Kennedy,et al.  Regulation of brain Type II Ca 2+ calmodulin -dependent protein kinase by autophosphorylation: A Ca2+-triggered molecular switch , 1986, Cell.