Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons

Abstract

The rules by which neuronal activity causes long-term modification of synapses in the central nervous system are not fully understood. Whereas competitive or correlation-based rules result in local modification of synapses, homeostatic modifications allow neuron-wide changes in synaptic strength, promoting stability. Experimental investigations of these rules at central nervous system synapses have relied generally on manipulating activity in populations of neurons. Here, we investigated the effect of suppressing excitability in single neurons within a network of active hippocampal neurons by overexpressing an inward-rectifier potassium channel. Reducing activity in a neuron before synapse formation leads to a reduction in functional synaptic inputs to that neuron; no such reduction was observed when activity of all neurons was uniformly suppressed. In contrast, suppressing activity in a single neuron after synapses are established results in a homeostatic increase in synaptic input, which restores the activity of the neuron to control levels. Our results highlight the differences between global and selective suppression of activity, as well as those between early and late manipulation of activity.

GABA A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

“…To address such a possibility, one would need to block either activity or neurotransmission, but not both. Recent studies have demonstrated that neither hyperpolarization nor reducing spike rate in the postsynaptic cell leads to compensatory changes in mPSC amplitude as would be predicted by the cell activity model (8,(16)(17)(18)(19). In those studies, the release and binding of neurotransmitters to their receptors was not altered, and thus the results are consistent with the neurotransmitter model.…”

“…Once GABA A transmission is no longer depolarizing, it may not be able to trigger the same downstream cascades, and the role of triggering compensatory quantal changes may be transferred to AMPAergic transmission. In four separate studies (in vitro and in vivo), activity was reduced in only the postsynaptic cell by expression of a potassium channel, whereas neurotransmitter release by the cell inputs remained intact and presumably unaltered (16)(17)(18)(19). Although some of these studies reported a compensatory change in probability of release, none of them observed the expected increase in quantal amplitude.…”

Role of pre- and postsynaptic activity in thalamocortical axon branching

“…The PCR product was inserted into the pCAGGS vector. To generate nonconducting kir2.1 mutant, the pore-region amino acid motif GYG was mutated to AAA (16). Cotransfection of pCAGGS-eyfp and pCAGGS-kir2.1 (or pCAGGS-kir2.1 mutant) was performed for organotypic coculture preparations to examine the detail of axon morphology.…”

“…To do this, neural activity of either thalamic or cortical cells was selectively silenced by means of overexpression of Kir2.1, an inward rectifying potassium channel (16,17). Our findings suggest that TC axon branching is inhibited by reducing the activity at either of these locations, suggesting that both pre-and postsynaptic activity is required for the development of TC axon branching.…”

Effects of chronic network hyperexcitability on the growth of hippocampal dendrites

“…Experiments have consistently shown that increased neuronal activity, produced by chronic disinhibition, results in diminished glutamatergic synaptic transmission (Turrigiano et al, 1998;O'Brien et al, 1998;Watt et al, 2000). However, with few exceptions (Desai et al, 2002;Burrone et al, 2002;Wierenga et al, 2006) these studies were not explicitly designed to determine the impact of persistent hyperexcitability on neuronal growth and maturation.…”