Timing dependent potentiation and depression of electrical synapses contributes to network stability in the crustacean cardiac ganglion.

Central pattern generators produce many rhythms necessary for survival (e.g., chewing, breathing, locomotion) and doing so often requires coordination of neurons through electrical synapses. Because even neurons of the same type within a network are often differentially tuned, uniformly applied neuromodulators or toxins can result in uncoordinated activity. In the crab (Cancer borealis) cardiac ganglion, potassium channel blockers and serotonin cause increased depolarization of the five electrically coupled motor neurons as well as loss of the normally completely synchronous activity. Given time, compensation occurs that restores excitability and synchrony. One of the underlying mechanisms of this compensation is an increase in coupling among neurons. However, the salient physiological signal that initiates increased coupling has not been determined. Using male C. borealis, we show that it is the loss of synchronous voltage signals between coupled neurons that is at least partly responsible for plasticity in coupling. Shorter offsets in naturalistic activity across a gap junction enhance coupling, while longer delays depress coupling. We also provide evidence as to why a desynchronization-specific potentiation or depression of the synapse could ultimately be adaptive through using a hybrid network created by artificially coupling two cardiac ganglia. Specifically, a stray neuron may be "brought back" in line by increasing coupling if its activity is closer to the remainder of the network. However, if a neuron's activity is far outside network parameters, it is detrimental to increase coupling and therefore depression of the synapse removes a potentially harmful influence on the network.SIGNIFICANCE STATEMENTUnderstanding how neural networks maintain output over years despite environmental and physiological challenges requires understanding the regulatory principles of these networks. Here we study how cells that are synchronously active at baseline respond to becoming desynchronized. In this system, a loss of synchrony causes different parts of the heart to receive uncoordinated stimulation. We find a calcium-dependent control mechanism which alters the strength of electrical connections between motor neurons. While others have described similar control mechanisms, here we demonstrate that voltage changes are sufficient to elicit regulation. Furthermore, we demonstrate that strong connections in a sufficiently perturbed network can prevent any neuron from producing its target activity, thus suggesting why the connections are not constitutively as strong as possible.