Interplay between population firing stability and single neuron dynamics in hippocampal networks

Abstract

Neuronal circuits' ability to maintain the delicate balance between stability and flexibility in changing environments is critical for normal neuronal functioning. However, to what extent individual neurons and neuronal populations maintain internal firing properties remains largely unknown. In this study, we show that distributions of spontaneous population firing rates and synchrony are subject to accurate homeostatic control following increase of synaptic inhibition in cultured hippocampal networks. Reduction in firing rate triggered synaptic and intrinsic adaptive responses operating as global homeostatic mechanisms to maintain firing macro-stability, without achieving local homeostasis at the single-neuron level. Adaptive mechanisms, while stabilizing population firing properties, reduced short-term facilitation essential for synaptic discrimination of input patterns. Thus, invariant ongoing population dynamics emerge from intrinsically unstable activity patterns of individual neurons and synapses. The observed differences in the precision of homeostatic control at different spatial scales challenge cell-autonomous theory of network homeostasis and suggest the existence of network-wide regulation rules.DOI: http://dx.doi.org/10.7554/eLife.04378.001

GABA B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

“…S1). Moreover, a GABA B R agonist, baclofen, triggered a pronounced block of firing rate that was precisely restored to the baseline level after a period of 2 d (9). The observed compensatory responses to increase in spiking activity by GABA A R antagonist or decrease in spiking activity by GABA B R agonist confirm the idea that homeostatic mechanisms maintain stable circuit function by keeping neuronal firing rate around a "set point" (10,18).…”

“…Given a pronounced effect of TTX 48h on spike-evoked synaptic vesicle exocytosis, these results suggest complete blockade of spikes does not trigger compensatory changes in spontaneous vesicle release. In previous studies, mEPSC frequency was found to be immune to chronic TTX treatment in some cases (18,41), while being up-regulated by AMPA receptor blockade (36,41), either by suppression of neuronal excitability (38) or by increase in the GABA B R-mediated inhibition (9). Thus, the induction of presynaptic homeostatic changes may require minimal spiking activity (41).…”

“…Spike sorting and analysis are described in ref. 9 and in SI Appendix, Spike Sorting and Data Analysis.…”

“…These stabilizing mechanisms have been collectively termed homeostatic plasticity. Homeostatic mechanisms enable invariant firing rates and patterns of neural networks composed from intrinsically unstable activity patterns of individual neurons (9).…”

Integrating Hebbian and homeostatic plasticity: introduction

“…The question is raised of whether cells have their own set points or whether the circuit as a whole maintains a set point to which each individual neuron contributes, but from a different set point at any given time. Slomowitz et al [14] originally found evidence that individual cells increased or decreased their firing rate to different values but the ensemble average was maintained at a set point [14]. In contrast, Hengen et al [15] recently showed that cells in visual cortex return to within 15% of their own set points following perturbation even though they start from widely differing initial firing rates.…”