Heterosynaptic Plasticity Prevents Runaway Synaptic Dynamics

Abstract

Spike timing-dependent plasticity (STDP) and other conventional Hebbian-type plasticity rules are prone to produce runaway dynamics of synaptic weights. Once potentiated, a synapse would have higher probability to lead to spikes and thus to be further potentiated, but once depressed, a synapse would tend to be further depressed. The runaway synaptic dynamics can be prevented by precisely balancing STDP rules for potentiation and depression; however, experimental evidence shows a great variety of potentiation and depression windows and magnitudes. Here we show that modifications of synapses to layer 2/3 pyramidal neurons from rat visual and auditory cortices in slices can be induced by intracellular tetanization: bursts of postsynaptic spikes without presynaptic stimulation. Induction of these heterosynaptic changes depended on the rise of intracellular calcium, and their direction and magnitude correlated with initial state of release mechanisms. We suggest that this type of plasticity serves as a mechanism that stabilizes the distribution of synaptic weights and prevents their runaway dynamics. To test this hypothesis, we develop a cortical neuron model implementing both homosynaptic (STDP) and heterosynaptic plasticity with properties matching the experimental data. We find that heterosynaptic plasticity effectively prevented runaway dynamics for the tested range of STDP and input parameters. Synaptic weights, although shifted from the original, remained normally distributed and nonsaturated. Our study presents a biophysically constrained model of how the interaction of different forms of plasticity-Hebbian and heterosynaptic-may prevent runaway synaptic dynamics and keep synaptic weights unsaturated and thus capable of further plastic changes and formation of new memories.

Direct Current Stimulation Alters Neuronal Input/Output Function

“…Both compartments are described by active and passive conductances following Hodgkin Huxley formalism. All the channel dynamics and transition rates are described in [31], [32], [34], [35]. Figure 2D shows a schematic representation of the model as well as its coupling to the extracellular field through the extracellular potential difference V E .…”

Heterosynaptic Plasticity

“…We used computer models to test the hypothesis that heterosynaptic plasticity observed in intracellular tetanization experiments can prevent runaway dynamics of synaptic weights and activity (Chen and others 2013b). The model neuron consisted of two compartments, axosomatic and dendritic, and received synaptic inputs from 100 simulated presynaptic neurons (Fig.…”

“…Data for N = 136 inputs to pyramidal neurons in slices of visual cortex (N = 60 inputs) and auditory cortex (N = 76 inputs). Green symbols (star, square, and triangle) refer to the example inputs from B (Modified, with permission, from Chen and others 2013b). …”

“…Instead, synaptic weights reached a new balance and formed a normal distribution around a new mean. Conventions as in B (Modified, with permission, from Chen and others 2013b). …”

“…Most STDP rules, including examples shown in the bottom, led to runaway dynamics of synaptic weights. In contrast, model with STDP and heterosynaptic plasticity ( C ) did not express runaway dynamics over the whole range of tested STDP rules, including those extremely unbalanced (insets, bottom) (Modified, with permission, from Chen and others 2013b). …”