E Pluribus Unum: Principles and Plasticity of Electrical Coupling in a Neuronal Network

The complex network activity patterns of the CNS result from an interplay between intrinsic neuronal properties and the connections formed by component cells. Connectivity is most commonly considered in terms of the classical chemical synapse.

It is now clear, however, that electrical synapses formed by intercellular connexin channels in gap junctions (GJs) are widespread in the mammalian CNS and critically influence circuit activity.

But exactly how GJs shape brain output, and how electrical coupling is regulated over different time-scales remains elusive.In the proposed project, we will take advantage of a recently discovered species difference between hypothalamic tuberoinfundibular dopamine (TIDA) neurons in the rat and mouse, to address these issues.

In the rat, TIDA neurons are connected by strong GJs and exhibit a slow network oscillation; in the mouse the same cells completely lack electrical synapses and oscillate faster, a difference that ultimately leads to different male parenting phenotypes.

Using the TIDA system as a platform, we will examine:I) What happens to TIDA neuronal properties and the male paternal circuit when GJs are removed from the coupled circuit, or when uncoupled cells are joined by electrical synapses?II) Does the pregnant dam prepare for motherhood by decoupling the TIDA network?III) Does electrical coupling fluctuate across neuronal oscillations?

What are the mechanisms and consequences for circuit output?IV) Which organizing principles are conferred onto a network by the presence of GJs?These issues will be addressed by a combination of in vitro electrophysiology, imaging, voltammetry, behavioural paradigms and molecular analysis for a comprehensive investigation of GJ function and modulation.

By leveraging the unique “experiment of nature” offered by the rodent TIDA system, the proposed project will address core issues of electrical coupling that have long remained out of reach for experimental scrutiny.