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I am reading this paper and I have come across the following statement:

"We sought to test whether exogenous Kirrel3 expression induces synapse formation via a gain-of-function assay... Because most CA1 neurons do not express Kirrel3, we used this in vitro specificity to our advantage and tested whether exogenous Kirrel3 expression in CA1 neurons could induce ectopic DG-to-CA1 synapses".

In the above statement, I am trying to figure out what is meant by a "gain-of-function assay".

I have searched online for a definition for gain-of-function, and all the search results talk about it in the context of virology, e.g. this paper states:

"Gain-of-function (GOF) research involves experimentation that aims or is expected to (and/or, perhaps, actually does) increase the transmissibility and/or virulence of pathogens"

I was wondering, in the context of neuroscience research, what is a gain-of-function assay? In this context, does it simply refer to the fact that the researchers overexpressed Kirrel3 in CA1 neurons (which normally do not express Kirrel3)?

Any advice is appreciated.

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  • $\begingroup$ The function in this case is the formation of synapses. $\endgroup$ Mar 1, 2022 at 10:23

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Nothing special is meant here except the standard English meaning of these words.

The second half of the quoted passage explains what they intend to do:

Because most CA1 neurons do not express Kirrel3, we used this in vitro specificity to our advantage and tested whether exogenous Kirrel3 expression in CA1 neurons could induce ectopic DG-to-CA1 synapses

To find out what Kirrel3 does, they're going to add Kirril3 ("exogenous...expression") and see what happens, and use that to infer something about the function of Kirril3. The cells that don't normally have Kirill3 are gaining its function. The opposite approach would be to remove Kirril3 from someplace that it normally is, which you could call "loss of function" - that might be a knockout animal, RNAi, use of an antagonist or other pharmacological manipulation, etc.

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