In order to implement the objectives of this project, we have first recruited new highly qualified members to the group following international advertising, purchased several state-of-the-art pieces of equipment and established a series of new techniques in the laboratory. These investments, made possible by the generous support of the ERC, have made it possible for us to make progress related to all the objectives. – In one project, we are performing a “species conversion” by introducing electrical synapses to mouse TIDA neurons (which normally lack such connections) and, in parallel, dissolving these intercellular channels between rat TIDA neurons, a system where electrical synapses normally are abundant. The latter (rat) part is still in initial stages but for the mouse project, we were able to accomplish some level of connectivity which support our hypotheses of electrical synapses and their role in network operation in a novel way. At the same time, the fact that a full functional “species conversion” was not achieved suggests the existence of (as yet unknown) additional components required for the formation of electrical connectivity, which is being followed up by a new series of experiments. Secondly, we have discovered that in female rats, the normally strongly coupled TIDA system dissolves its electrical synapses during pregnancy in what we interpret as an adaptation to motherhood. This is a novel finding that suggests, among other things, that gap junctions are highly dynamic constructs and that they can be added or removed as the life conditions of an animal changes. Thirdly, since rat TIDA neurons undergo a highly regular oscillation with a period of ca 3 secs, we are examining if and how electrical synapses alter their strength across the oscillation cycle. Indeed, even at this brief time scale, neurons alter their coupling strength such that they are maximally connected when the period of electrical discharge commences. Fourth, we are exploring how the passage of current can be asymmetrical, i.e. stronger from one cell to another than in the opposite direction of the same pair. Our experiments suggest that this may be caused by the expression of multiple types of gap junction proteins within the pair, including proteins that previously were believed to be absent from neurons. In addition, we have also discovered how TIDA neurons are regulated by estrogen, that could explain why this sex hormone is such a powerful release-promoting agent for the hormone, prolactin, which plays a key role in maternal behaviour and reproduction, and how TIDA neurons are regulated by the brain’s main excitatory transmitter, glutamate, through a number of parallel paths.
