Population bursts in a modular neural network as a mechanism for synchronized activity in KNDy neurons

PLoS Comput Biol. 2024 Jul 31;20(7):e1011820. doi: 10.1371/journal.pcbi.1011820. eCollection 2024 Jul.

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 on synchronization of changes in the coupling strength within clusters versus between clusters.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Computational Biology
  • Computer Simulation
  • Dynorphins* / metabolism
  • Dynorphins* / physiology
  • Gonadotropin-Releasing Hormone* / metabolism
  • Humans
  • Kisspeptins / metabolism
  • Kisspeptins / physiology
  • Models, Neurological*
  • Nerve Net* / physiology
  • Neurokinin B / metabolism
  • Neurokinin B / physiology
  • Neurons* / physiology

Substances

  • Dynorphins
  • Gonadotropin-Releasing Hormone
  • Kisspeptins
  • Neurokinin B

Grants and funding

W. B. was partially supported by grant number 200551/2022-1 from the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico - CNPq, https://www.gov.br/cnpq). J. T. was supported by grants BB/X005038/1 and EP/V048716/1 from United Kingdom Research and Innovation (UKRI), https://www.ukri.org. R. B. was supported by National Science Foundation grant DMS 2324962, https://www.nsf.gov/. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.