Abstract
SummaryLong-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression—pre- or postsynaptic—is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity.
Highlights
Our brain must retain accurate memories of past events
The combined effect of presynaptic release and subsequent postsynaptic detection of neurotransmitters on the postsynaptic membrane potential has been formalized as a (Binomial) stochastic process whose mean and variance depend on Prel, N and q, such that mean = NqPrel and variance = Nq2Prelð1 À PrelÞ
We introduce a theoretical framework in which such variability is explained as a consequence of a gradual optimization of the postsynaptic responses’ distribution toward a higher or lower bound, i.e., the most reliable, strongest possible synapse in the case of potentiation, or the most reliable, weakest synapse in the case of depression (Figure 1C and Movie S1)
Summary
Our brain must retain accurate memories of past events. Reliable memory storage is believed to depend on long-term modifications in synaptic transmission (Gruart et al, 2006; Nabavi et al, 2014; Costa et al, 2017). The amplitude of postsynaptic responses can be changed through various long-term plasticity protocols Such changes show a high degree of variability of pre- and postsynaptic modifications, i.e., in Prel and q, respectively (Larkman et al, 1992; Bolshakov and Siegelbaum, 1995; Zakharenko et al, 2001; Bayazitov et al, 2007; Lisman and Raghavachari, 2006; Sjostrom et al, 2007; Loebel et al, 2013; Bliss and Collingridge, 2013; Costa et al, 2017; with N being stable within the timescale studied here, $1 hr [Bolshakov et al, 1997; Saez and Friedlander, 2009], but see Discussion). No theory has been proposed to explain the long standing riddle of high variability in the expression loci of long-term synaptic plasticity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
