Modulation of network behaviour by changes in variance in interneuronal properties

Abstract

Interneurones are important regulators of neuronal networks. The conventional approach to interneurones is to focus on the mean values of various parameters. Here we tested the hypothesis that changes in the variance of interneuronal properties (e.g. in the degree of scattering of parameter values of individual cells around the population mean) may modify the behaviour of networks. Biophysically based multicompartmental models of principal cells and interneurones showed that changes in the variance in the electrophysiological and anatomical properties of interneurones significantly alter the input-output functions, rhythmicity and synchrony of principal cells, even if the mean values were unchanged. In most cases, increased heterogeneity in interneurones resulted in stronger inhibition of principal cell firing; however, there were parameter ranges where increased interneuronal variance decreased the inhibition of principal cells. Electrophysiological recordings showed that the variance in the resting membrane potential of CA1 stratum oriens interneurones persistently increased following experimental complex febrile seizures in developing rats, without a change in the mean resting membrane potential, indicating that lasting alterations in interneuronal heterogeneity can take place in real neuronal systems. These computational and experimental data demonstrate that modifications in interneuronal population variance influence the behaviour of neuronal networks, and suggest a physiological role for interneuronal diversity. Furthermore, the results indicate that interneuronal heterogeneity can change in neurological diseases, and raise the possibility that neuromodulators may act by regulating the variance of key parameters in interneuronal populations. (approx. 4 %) (Buhl et al. 1994 a; Halasy et al. 1996). Even in the case of the axo-axonic cell, which is considered to be the most stereotyped interneurone, about 10 % of the postsynaptic targets can include somata and proximal dendrites (Buhl et al. 1994 a). Variability also exists in the number of terminals given by a single interneurone onto a single principal cell (range for axo-axonic cells: 2-15 terminals per initial segment; Li et al. 1992; Han et al. 1993; for basket cells: 2-10 synapses; Gulyás et al. 1993; Buhl et al. 1994 a; Miles et al. 1996).This study tested the hypothesis that changes in the variability in interneuronal populations may have consequences in how interneuronal-principal cell networks interact. The simulation results indicate that heterogeneity in both the physiological and anatomical properties can influence the inhibitory control of principal cells. In addition, experimental evidence is presented to demonstrate that alterations in the variance (and not only in the mean) of interneuronal parameters can take place in hyperexcitable tissues. METHODSMulticompartmental modelling techniques were used to study principal cell-interneurone networks. (Hines & Carnevale, 1995), which shows second-order accuracy and robust numerical stability. The...

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