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

Abstract

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.

Neural oligarchy: how synaptic plasticity breeds neurons with extreme influence

“…Importantly, these distributions persist in the absence of activity and 479 activity-dependent changes (Fig. 10A-B, light coloured curves relating to TTX), in line 480 with experimental findings [6,23]. However, when µ we and µ wi are negative, weights 481 move away from their lognormal-like shape (Suppl.…”

“…Lognormal-like distributions have been observed in the weights of cortical [5,8] [18,23,56]). We conclude that I-E and E-E 344 weights in our network may form through the combination of potentiating STDP and 345 SN a right-skewed long-tailed distribution that resembles a lognormal distribution, but 346 as in the experimental observations, is not in fact precisely and entirely lognormal.…”

“…the contribution from the activity-dependent changes. Moreover, synapses continue to 471 change in the presence of TTX, which abolishes spiking activity [6,23].…”

Insufficient developmental excitatory neuronal activity fails to foster establishment of normal levels of inhibitory neuronal activity

“…Alteration of excitatory and inhibitory synapses continues to be modulated during postnatal development (Carstens et al, 2016;Wang and Fawcett, 2012). The delay in establishment of inhibitory activity promotes synaptic plasticity but also allows a developmental window of increased seizure activity (Briggs and Galanopoulou, 2011;Esclapez et al, 1999;Gu et al, 2016;Luhmann and Prince, 1991;Rubinski and Ziv, 2015;Sutor and Luhmann, 1995). Inhibitory neuronal activity is thought to be triggered during development by progressively increasing excitatory activity (Marty et al, 2000;Seil, 1999;Spitzer, 2006;Zhang and Poo, 2001).…”

Lifetime of a structure evolving by cluster aggregation and particle loss, and application to postsynaptic scaffold domains

“…The model of ref. [3] can be experimentally distinguished from other ones [28][29][30] on different grounds. First, at the most basic level, it supposes that the existence of a scaffold domain depends on a lateral flux of scaffolding proteins onto the domain.…”