Elsevier

Neuroscience

Volume 122, Issue 3, 2003, Pages 811-829
Neuroscience

Synaptic background noise controls the input/output characteristics of single cells in an in vitro model of in vivo activity

https://doi.org/10.1016/j.neuroscience.2003.08.027Get rights and content

Abstract

In vivo, in vitro and computational studies were used to investigate the impact of the synaptic background activity observed in neocortical neurons in vivo. We simulated background activity in vitro using two stochastic Ornstein-Uhlenbeck processes describing glutamatergic and GABAergic synaptic conductances, which were injected into a cell in real time using the dynamic clamp technique. With parameters chosen to mimic in vivo conditions, layer 5 rat prefrontal cortex cells recorded in vitro were depolarized by about 15 mV, their membrane fluctuated with a S.D. of about 4 mV, their input resistances decreased five-fold, their spontaneous firing had a high coefficient of variation and an average firing rate of about 5–10 Hz. Brief changes in the variance of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synaptic conductance fluctuations induced time-locked spiking without significantly changing the average membrane potential of the cell. These transients mimicked increases in the correlation of excitatory inputs. Background activity was highly effective in modulating the firing-rate/current curve of the cell: the variance of the simulated γ-aminobutyric acid (GABA) and AMPA conductances individually set the input/output gain, the mean excitatory and inhibitory conductances set the working point, and the mean inhibitory conductance controlled the input resistance. An average ratio of inhibitory to excitatory mean conductances close to 4 was optimal in generating membrane potential fluctuations with high coefficients of variation. We conclude that background synaptic activity can dynamically modulate the input/output properties of individual neocortical neurons in vivo.

Section snippets

In vivo experiments

The methods used in the in vivo preparations are similar to those described elsewhere (Henze et al., 2000). Three Sprague–Dawley rats (300–500 g) were anesthetized with urethane (1.65 g/kg; Sigma) and placed in a stereotaxic apparatus (Kopf, Tujunga, CA, USA). The body temperature of the rat was monitored and kept around 35 °C. A small portion of the skull was drilled (about 1 mm×1 mm) above the pre-limbic/infra-limbic areas of the prefrontal cortex (2.0 mm anterior from Bregma, 1.0 mm lateral,

Recreation of in vivo-like activity

Intracellularly recorded (n=5) layer 5 pyramidal cells of rat prefrontal cortex in vivo under urethane anesthesia exhibit large fluctuations in their membrane potentials, accompanied by occasional spontaneous discharges (Fig. 1A). These membrane fluctuations had a S.D. of about 4 mV (3.9±0.5 mV; n=4), the average membrane potential was around −65 mV (−65±2.6 mV; n=4), and the spontaneous discharge rate was highly irregular with a CV around 1 (0.94±0.17; n=4) and an average firing rate of about

Discussion

Although the properties of neurons recorded in vitro are quite different from those recorded in vivo, they were much more similar when neurons in vitro were stimulated with two stochastic processes simulating excitatory and inhibitory conductances. We used the dynamic clamp technique to inject these conductances in layer 5 pyramidal cells of the rat prefrontal cortex. As a consequence, cells were depolarized by about 15 mV, their input resistances were decreased four-five-fold, and their

Acknowledgements

We thank Darrel Henze and G. Buzsaki (Rutgers University) for their invaluable help with the in vivo experiments. Research was supported by the Howard Hughes Medical Institute, the National Institutes of Health (NIH) and the Centre National pour la Recherche Scientifique (CNRS).

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