Remodeling and Tenacity of Inhibitory Synapses: Relationships with Network Activity and Neighboring Excitatory Synapses

Glutamatergic synapse size remodeling is governed not only by specific activity forms but also by apparently stochastic processes with well-defined statistics. These spontaneous remodeling processes can give rise to skewed and stable synaptic size distributions, underlie scaling of these distributions and drive changes in glutamatergic synapse size “configurations”. Where inhibitory synapses are concerned, however, little is known on spontaneous remodeling dynamics, their statistics, their activity dependence or their long-term consequences. Here we followed individual inhibitory synapses for days, and analyzed their size remodeling dynamics within the statistical framework previously developed for glutamatergic synapses. Similar to glutamatergic synapses, size distributions of inhibitory synapses were skewed and stable; at the same time, however, sizes of individual synapses changed considerably, leading to gradual changes in synaptic size configurations. The suppression of network activity only transiently affected spontaneous remodeling dynamics, did not affect synaptic size configuration change rates and was not followed by the scaling of inhibitory synapse size distributions. Comparisons with glutamatergic synapses within the same dendrites revealed a degree of coupling between nearby inhibitory and excitatory synapse remodeling, but also revealed that inhibitory synapse size configurations changed at considerably slower rates than those of their glutamatergic neighbors. These findings point to quantitative differences in spontaneous remodeling dynamics of inhibitory and excitatory synapses but also reveal deep qualitative similarities in the processes that control their sizes and govern their remodeling dynamics.Author Summary: Synaptic plasticity is widely believed to constitute a fundamental mechanism for altering network function. An (implicit) extension of this belief is an assumption that spontaneous changes in synaptic function should not occur to any significant degree. Where excitatory synapses are concerned, recent studies have questioned the validity of this assumption. Where inhibitory synapses are concerned, however, much less is known. Here we followed the spontaneous remodeling dynamics of inhibitory synapses for days, and analyzed these dynamics within a statistical framework previously developed for glutamatergic synapses. Like their excitatory counterparts, sizes of individual synapses fluctuated considerably. Similarly, these spontaneous fluctuations were governed by a well-defined statistical process which assures that synaptic size distributions remain constant. Contrary to the aforementioned assumption, these spontaneous fluctuations drove changes in synaptic size configurations; interestingly, however, change rates were slower for inhibitory synapses. Unlike excitatory synapses, suppressing network activity barely affected inhibitory synapse remodeling dynamics, synaptic configuration change rates or synaptic size distributions. Our findings thus point to quantitative differences in spontaneous remodeling dynamics of inhibitory and excitatory synapses, but also indicate that the processes that control their sizes and govern their remodeling dynamics are fundamentally similar.