Content area
Full text
About the Authors:
Alon Poleg-Polsky
* E-mail: [email protected]
Affiliation: Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
Jeffrey S. Diamond
Affiliation: Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
Introduction
Most neurons receive myriad excitatory and inhibitory synaptic inputs in complex spatial-temporal patterns. The dynamic balance between excitation and inhibition (E/I) is important in determining neural activity, but is hard to detect directly. Among a number of indirect techniques used to detect synaptic composition, one of the most popular is the somatic single electrode voltage clamp, which has been applied in a wide variety of in-vivo and in-vitro preparations.
The E/I balance can be calculated from recorded currents with a number of different methods. The first technique assumes that, when the cell is clamped at either the excitatory or the inhibitory reversal potential, the respective synaptic drive is neutralized and doesn't contribute to the recorded current at the electrode. By recording sequentially excitatory and inhibitory currents it is presumably possible to determine whether the E/I balance changes between different conditions [1], [2], [3], [4].
A second technique involves a more involved analysis of synaptic conductances obtained from synaptic IV relations. First, postsynaptic currents are recorded over a number of different holding potentials. The total synaptic conductance is determined from the slope of the resulting IV curve and the E/I ratio is calculated based on the reversal potential of the curve [4], [5], [6], [7]. This method explicitly assumes an arithmetic integration of the synaptic input by the recorded cell [8], [9].
Both approaches implicitly presume that voltage clamp prevents any form of shunting inhibition in the postsynaptic membrane. However, the site of synaptic activation often is distant from the recording site, and previous studies have demonstrated that somatic voltage clamp exerts limited voltage control across the dendritic arbor [10], [11], [12], [13], [14]. In a realistic neuronal morphology, the expected poor space clamp cannot prevent synaptic inputs from driving the membrane potential away from the holding potential [12], [14], [15]. In these conditions inhibitory inputs can influence EPSCs even when the cell is apparently clamped at the inhibitory reversal potential [16].