Neuroscience Research 41 (2001) 161 – 183 www.elsevier.com/locate/neures Dendritic spatial flicker of local membrane potential due to channel noise and probabilistic firing of hippocampal neurons in culture Leonid P. Savtchenko a,b,1 , Paul Gogan a , Suzanne Tyc ˇ-Dumont a, * a Unite ´ de Neurocyberne ´tique Cellulaire, 280 Bd Sainte Marguerite, 13009 Marseille, France b Research Laboratory of Biophysics and Bioelectronics, International Center for Molecular Physiology (Dniepropetrosk diision), National Academy of Sciences of Ukraine, Dniepropetrosk State Uniersity, Dniepropetrosk 49050, Ukraine Received 16 March 2001; accepted 16 July 2001 Abstract Whole-cell recordings and imaging of dissociated hippocampal neurons stained with voltage sensitive dye provide a new microscopic picture of neuronal excitation. This is the first attempt to combine imaging of active channel clusters on the geometry of live neurons and a theoretical approach. During single somatic action potentials and the back-invasion into the neurites, local mean potentials are generated at sites of active channel clusters which are unevenly distributed in the neuronal membrane. Similar mean membrane potentials are observed in the neurites and at the soma. Identical action potentials produce different spatial patterns of mean membrane potentials from trial to trial. This spatial variability is explained by the stochastic behavior of the channels in the clusters. When hippocampal neurons are excited by synaptic inputs, their evoked responses are probabilistic and generate variable spatial patterns of mean membrane potential trial after trial. Our stochastic model reproduces this random behavior by assuming that the voltage fluctuations generated by channel noise are added to the synaptic potentials reaching the soma. We demonstrate that the probability of action potential initiation depends on the strength of the synaptic input, the diameter of the dendrites and the relative positions of the channel clusters, of the synapse and of the soma. © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. Keywords: Hippocampal neurons; Active channel clusters; Imaging; Probabilistic synaptic firing; Dendritic back-invasion; Stochastic model 1. Introduction The dendritic membrane of some types of vertebrate central neurons contains active conductances that are important to process synaptic inputs and shape the output frequency discharges of the neuron. Recent ex- perimental data came from dendritic patch recordings in slice experiments describing active Na + ,K + and Ca ++ channels in membrane patches of dendrites of pyramidal neurons from hippocampus and neocortex (for review see Yuste and Tank, 1996; Johnston et al., 1996). This evidence has led to suggestions that these voltage dependent channels can boost distal synaptic events, affect synaptic integration locally and modulate synaptic efficacy by coincidence of EPSP and back-in- vading action potentials (Stuart and Sakmann, 1995). Information about the position of these conductances and their operations in a tree when the neuron is excited is crucial for the understanding of their func- tional role in dendritic processing (Mel, 1993). Yet, the study of the spatial distribution of voltage- dependent ionic conductances over a large portion of a dendrite, their kinetics and their voltage dependencies remains limited by the technical hurdles that render direct experimental verification of hypothesis extremely difficult. Even dual somatic and dendritic patch record- ings from restricted membrane patches of the same neuron suffer from spatial limitation and yield insuffi- cient view of all electrical events that occur in the * Corresponding author. Tel.: +33-491-75-0200; fax: +33-491-26- 2038. E-mail address: tycdum@marseille.inserm.fr (S. Tyc ˇ-Dumont). 1 Associated researcher at CNRS. 0168-0102/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. PII:S0168-0102(01)00274-7