Abstracts

RATIONALE: Interneurones are important regulators of neuronal excitability. The conventional approach to describing interneuronal properties 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 neural activity in networks of inhibitory and excitatory cells. Following this presentation the participants should be able to discuss the importance of changes in interneuronal variability and its possible relevance in epilepsy research.
METHODS: Biophysically realistic multicompartmental models of principal cells and interneurones were constructed that incorporated experimentally determined values of parameters measured from hippocampal interneurons and CA1 pyramidal cells. Inhibitory synaptic inputs to principal cells and excitatory inputs to interneurons were described by using exponentials to reproduce the amplitudes and kinetics of IPSPs and EPSPs (Chen et al., Nat. Med. 2001; Aradi and Soltesz, J. Physiol. 2002).
RESULTS: The results showed that changes in the variance in the electrophysiological (i.e. adaptation properties, resting membrane potential) and anatomical properties (axonal arborization) 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. These simulation results showed that the degree of interneuronal variability can be an important factor in controlling neuronal excitability. 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. These experimental findings indicate that lasting alterations in interneuronal heterogeneity can take place in real neuronal systems.
CONCLUSIONS: These computational and experimental data demonstrate that modifications in interneuronal population variance influence the excitability of neuronal networks suggesting a physiological role for interneuronal variability. Furthermore, the results indicate that interneuronal heterogeneity can change in seizure models, and raise the possibility that neuromodulators may act by regulating the variance of different properties in interneuronal populations.
[Supported by: NIH (NS35915) to I.S. and Fellowship of the Epilepsy Foundation of America to I.A.]