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Activity-dependent scaling of quantal amplitude in neocortical neurons

Abstract

Information is stored in neural circuits through long-lasting changes in synaptic strengths1,2. Most studies of information storage have focused on mechanisms such as long-term potentiation and depression (LTP and LTD), in which synaptic strengths change in a synapse-specific manner3,4. In contrast, little attention has been paid to mechanisms that regulate the total synaptic strength of a neuron. Here we describe a new form of synaptic plasticity that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity. Chronic blockade of cortical culture activity increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) without changing their kinetics. Conversely, blocking GABA (γ-aminutyric acid)-mediated inhibition initially raised firing rates, but over a 48-hour period mESPC amplitudes decreased and firing rates returned to close to control values. These changes were at least partly due to postsynaptic alterations in the response to glutamate, and apparently affected each synapse in proportion to its initial strength. Such ‘synaptic scaling’ may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs5, as well as stabilizing synaptic strengths during Hebbian modification6,7 and facilitating competition between synapses7,8,9.

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Figure 1: AMPA mEPSC amplitudes from control cultures or cultures grown in TTX, CNQX or bicuculline for 48 hours.
Figure 2: Effects of activity on mEPSCs, paired transmission, and firing rates.
Figure 3: Activity blockade increases the postsynaptic sensitivity to glutamate.
Figure 4: Activity scales mEPSC amplitudes multiplicatively.

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Acknowledgements

We thank H. Lauer for technical assistance, and L. F. Abbott, J. Lisman, E. Marder and M. Mauk for discussions and advice. This work was supported by the Whitehall Foundation, NSF, NIH and the Sloan Foundation. K.R.L. was supported by an HHMI predoctoral fellowship.

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Correspondence to Gina G. Turrigiano.

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Turrigiano, G., Leslie, K., Desai, N. et al. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391, 892–896 (1998). https://doi.org/10.1038/36103

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