Population Bursts in a Modular Neural Network as a Mechanism for Synchronized Activity in KNDy Neurons

Abstract

The pulsatile activity of gonadotropin-releasing hormone neurons (GnRH neurons) is a key factor in the regulation of reproductive hormones. This pulsatility is orchestrated by a network of neurons that release the neurotransmitters kisspeptin, neurokinin B, and dynorphin (KNDy neurons), and produce episodic bursts of activity driving the GnRH neurons. We show in this computational study that the features of coordinated KNDy neuron activity can be explained by a neural network in which connectivity among neurons is modular. That is, a network structure consisting of clusters of highly-connected neurons with sparse coupling among the clusters. This modular structure, with distinct parameters for intracluster and intercluster coupling, also yields predictions for the differential effects of the co-released transmitters neurokinin B and dynorphin. In particular, it provides one possible explanation for how the excitatory neurotransmitter neurokinin B and the inhibitory neurotransmitter dynorphin can both increase the degree of synchronization among KNDy neurons. Author summarySince the discovery of a small population of hypothalamic neurons that secrete kisspeptin, neurokinin B, and dynorphin (KNDy neurons), there has been interest in their role as a pacemaker for the pulsatile release of key reproductive hormones. A fundamental question is what mechanism coordinates KNDy neuron activity to generate population bursts. Optical imaging of the KNDy network at single-neuron resolution has revealed that individual KNDy neurons participate in many, but not all, population bursts. It has also shown that the order in which the neurons are recruited in each burst could be highly determined in some animals but not in others. We demonstrate here that these observations can be explained by a neural network with a modular structure. We also show how such a structure can explain the paradoxical finding that both the excitatory neurotransmitter neurokinin B and the inhibitory neurotransmitter dynorphin can act to increase the degree of synchronization among the KNDy neurons.