Homeostatic role of heterosynaptic plasticity: models and experiments

Abstract

Homosynaptic Hebbian-type plasticity provides a cellular mechanism of learning and refinement of connectivity during development in a variety of biological systems. In this review we argue that a complimentary form of plasticity—heterosynaptic plasticity—represents a necessary cellular component for homeostatic regulation of synaptic weights and neuronal activity. The required properties of a homeostatic mechanism which acutely constrains the runaway dynamics imposed by Hebbian associative plasticity have been well-articulated by theoretical and modeling studies. Such mechanism(s) should robustly support the stability of operation of neuronal networks and synaptic competition, include changes at non-active synapses, and operate on a similar time scale to Hebbian-type plasticity. The experimentally observed properties of heterosynaptic plasticity have introduced it as a strong candidate to fulfill this homeostatic role. Subsequent modeling studies which incorporate heterosynaptic plasticity into model neurons with Hebbian synapses (utilizing an STDP learning rule) have confirmed its ability to robustly provide stability and competition. In contrast, properties of homeostatic synaptic scaling, which is triggered by extreme and long lasting (hours and days) changes of neuronal activity, do not fit two crucial requirements for a hypothetical homeostatic mechanism needed to provide stability of operation in the face of on-going synaptic changes driven by Hebbian-type learning rules. Both the trigger and the time scale of homeostatic synaptic scaling are fundamentally different from those of the Hebbian-type plasticity. We conclude that heterosynaptic plasticity, which is triggered by the same episodes of strong postsynaptic activity and operates on the same time scale as Hebbian-type associative plasticity, is ideally suited to serve a homeostatic role during on-going synaptic plasticity.

Hebbian plasticity requires compensatory processes on multiple timescales

“…However, from a theoretical perspective, we expect that heterosynaptic effects caused by stimulation of one presynaptic pathway are weak when measured at only one ‘control’ synapse; a weak change at individual synapses could still have a strong accumulated effect over thousands of synapses. Therefore, even weak heterosynaptic plasticity could act as a strong RCP [40,103,118]. …”

“…Therefore, it is unclear whether the ‘burst-detector’ for heterosynaptic plasticity would be triggered [40,103,118]. …”

“…Heterosynaptic plasticity and heterosynaptic effects mediated through metaplasticity [23,120,143] are promising candidates to stabilize Hebbian plasticity models against runaway LTP [26,40,103,118]. While heterosynaptic plasticity has been observed in various experiments [39,117], a conclusive picture and data-driven models are still scarce.…”

Duration Dependent Effects of Transcranial Pulsed Current Stimulation (tPCS) Indexed by Electroencephalography

“…This might be associated to homeostatic mechanisms, which play an important role in maintaining neural activity within a physiological dynamic range . The presence of a destabilizing factor such as brain stimulation can alter the equilibrium of neural activity over time . In the aim to prevent neural states from a runaway excitation or quiescence, homeostatic plasticity appears as a counter‐regulatory mechanism for the neural network function.…”

The dialectic of Hebb and homeostasis

“…There are, for example, several forms of non-associative plasticity that appear to be competitive, but not necessarily homeostatic. An example of this would be heterosynaptic plasticity, in which LTP of one synapse can produce LTD of nearby neighbouring synapses [31]. In principle, if the amount of heterosynaptic LTD exactly matched the amount of homosynaptic LTP, and if the reverse were also true, such a mechanism could constrain total synaptic strength in a homeostatic manner-but such perfect matching has not been clearly demonstrated.…”