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To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon excitation laser scanning microscopy to directly image action-potential-mediated calcium influx in single varicosities of layer 2\/3 pyramidal neurons in acute brain slices. Our data show that single action potentials or bursts of action potentials reliably invade axonal arbors over a range of developmental ages (postnatal 10\u201324 days) and temperatures (24\u00b0C-30\u00b0C). Hyperpolarizing current steps preceding action potential initiation, protocols that had previously been observed to produce failures of action potential propagation in cultured preparations, were ineffective in modulating the spread of action potentials in acute slices. Our data show that action potentials reliably invade the axonal arbors of neocortical pyramidal neurons. Failures in synaptic transmission must therefore originate downstream of action potential invasion. We also explored the function of modulators that inhibit presynaptic calcium influx. Consistent with previous studies, we find that adenosine reduces action-potential-mediated calcium influx in presynaptic terminals. This reduction was observed in all terminals tested, suggesting that some modulatory systems are expressed homogeneously in most terminals of the same neuron.<\/jats:p>","DOI":"10.1073\/pnas.170278697","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:34:10Z","timestamp":1027694050000},"page":"9724-9728","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":128,"title":["Action potentials reliably invade axonal arbors of rat neocortical neurons"],"prefix":"10.1073","volume":"97","author":[{"given":"Charles L.","family":"Cox","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724; Department of Neurobiology, State University of New York, Stony Brook, NY 11794; and Department of Biological Computation, Bell Laboratories, Lucent Technologies, Murray Hill, NJ 07974"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winfried","family":"Denk","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724; Department of Neurobiology, State University of New York, Stony Brook, NY 11794; and Department of Biological Computation, Bell Laboratories, Lucent Technologies, Murray Hill, NJ 07974"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Tank","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724; Department of Neurobiology, State University of New York, Stony Brook, NY 11794; and Department of Biological Computation, Bell Laboratories, Lucent Technologies, Murray Hill, NJ 07974"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karel","family":"Svoboda","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724; Department of Neurobiology, State University of New York, Stony Brook, NY 11794; and Department of Biological Computation, Bell Laboratories, Lucent Technologies, Murray Hill, NJ 07974"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2000,8,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-02728-8"},{"key":"e_1_3_3_2_2","volume-title":"The Fine Structure of the Nervous System","author":"Peters A","year":"1991","unstructured":"A Peters, S L Palay, HD Webster The Fine Structure of the Nervous System (Oxford Univ. 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