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AbstractöTo investigate the basis of the £uctuating activity present in neocortical neurons in vivo, we have combined computational models with whole-cell recordings using the dynamic-clamp technique. A simpli¢ed`point-conductance' model was used to represent the currents generated by thousands of stochastically releasing synapses. Synaptic activity was represented by two independent fast glutamatergic and GABAergic conductances described by stochastic randomwalk processes. An advantage of this approach is that all the model parameters can be determined from voltage-clamp experiments. We show that the point-conductance model captures the amplitude and spectral characteristics of the synaptic conductances during background activity. To determine if it can recreate in vivo-like activity, we injected this point-conductance model into a single-compartment model, or in rat prefrontal cortical neurons in vitro using dynamic clamp. This procedure successfully recreated several properties of neurons intracellularly recorded in vivo, such as a depolarized membrane potential, the presence of high-amplitude membrane potential £uctuations, a low-input resistance and irregular spontaneous ¢ring activity. In addition, the point-conductance model could simulate the enhancement of responsiveness due to background activity.We conclude that many of the characteristics of cortical neurons in vivo can be explained by fast glutamatergic and GABAergic conductances varying stochastically. ß 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: computational models, pyramidal neurons, dynamic clamp, synaptic bombardment, high-conductance states, CV.Synaptic background activity is invariably present in intracellular recordings of neocortical neurons in vivo, and modeling studies have suggested that it may have important consequences on the integrative properties of these neurons (Barrett, 1975;Holmes and Woody, 1989;Bernander et al., 1991;Destexhe and Parë, 1999). Background activity is maximal during the active states of the brain, when cortical neurons ¢re spontaneously at relatively high rates (5^20 Hz in awake animals; see Hubel, 1959;Evarts, 1964;Steriade, 1978;Matsumura et al., 1988;Steriade et al., 2001). This highly £uctuating activity was simulated in vitro by injecting noisy current waveforms (Mainen and Sejnowski, 1995;Stevens and Zador, 1998;Fellous et al., 2001). This approach, however, does not take into account the conductance due to background activity.Given that the neocortex is characterized by a very dense synaptic connectivity (5000^60 000 excitatory synapses per neuron; Cragg, 1967; DeFelipe and Farin ¬ as, 1992), these cells could potentially experience considerable amounts of synaptic conductances during periods of intense network activity. A recent estimation of the electrophysiological parameters of background activity in cat parietal cortex in vivo (Parë et al., 1998) provided evidence for a`high-conductance' state (see also Borg-Graham et al., 1998). By combining intracellular recording...

Viral vectors are the most efficient tools for gene delivery, and the search for tissue-specific infecting viruses is important for the development of in vivo gene therapy strategies. The baculovirus Autographa californica nuclear polyhedrosis virus is widely used as a vector for expression of foreign genes in insect cells, and its host specificity is supposed to be restricted to arthropods. Here we demonstrate that recombinant A. californica nuclear polyhedrosis virus is efficiently taken up by human hepatocytes via an endosomal pathway. High-level reporter gene expression from heterologous promoters was observed in human and rabbit hepatocytes in vitro. Mouse hepatocytes and some other epithelial cell types are targeted at a considerably lower rate. The efficiency of gene transfer by baculovirus considerably exceeds that obtained by calcium phosphate or lipid transfection. These properties of baculovirus suggest a use for it as a vector for liver-directed gene transfer but highlight a potential risk in handling certain recombinant baculoviruses.