Functional sensory circuits built from neurons of two species

Chimeras of two different species are well known and regularly used in biology – immunologists commonly create “humanized mice” which have (to varying degrees) a human immune system. For about ten years, biologists have been exploring the consequences of putting human neurons into non-human brains (recent-ish example here) and have seen that neurons from (say) humans can survive in (say) mouse brains and even get inserted into working circuits.

This new paper (Functional sensory circuits built from neurons of two species) makes rat-mouse chimeras very early in development (blastocyst) and looks at the chimeric brains, in which large parts of the nervous system are rat but in a mouse. Paper is OA (but not marked as such) and here’s the abstract and highlights:

A central question for regenerative neuroscience is whether synthetic neural circuits, such as those built from two species, can function in an intact brain. Here, we apply blastocyst complementation to selectively build and test interspecies neural circuits. Despite approximately 10–20 million years of evolution, and prominent species differences in brain size, rat pluripotent stem cells injected into mouse blastocysts develop and persist throughout the mouse brain. Unexpectedly, the mouse niche reprograms the birth dates of rat neurons in the cortex and hippocampus, supporting rat-mouse synaptic activity. When mouse olfactory neurons are genetically silenced or killed, rat neurons restore information flow to odor processing circuits. Moreover, they rescue the primal behavior of food seeking, although less well than mouse neurons. By revealing that a mouse can sense the world using neurons from another species, we establish neural blastocyst complementation as a powerful tool to identify conserved mechanisms of brain development, plasticity, and repair.

–Rat stem cells develop in mouse blastocysts to broadly populate two-species brains
–Rat neurons develop synchronously and synapse with cognate mouse neurons
–Genetic models of circuit loss or silencing unveil rescue capacity of exogenous neurons
–Rat sensory neurons restore the primal behavior of food seeking to anosmic mice

I think there are two big new aspects here:

  1. The rat neurons were “reset” to a mouse developmental clock. This suggests that a very early progenitor cell (in the blastocyst) acquires much of its “identity” from the environment (the niche, it’s called) instead of being genetically hard-wired. (Note the word “much” – the paper shows that rat neurons do retain some of their rat-ness even when they start in a blastocyst.) That’s pretty interesting and surprising, IMO.

  2. The rat neurons could direct a mouse-specific behavior: “…a mouse can sense the world using neurons from another species.” This has not been shown before (that a chimeric brain could actually do that) and I think it’s interesting and again a little surprising.

Lots to think about and the authors plant some seeds, mentioning other types of senses in the first paragraph of the Introduction:

The genome is the ultimate architect of the brain. Its evolutionary variations enable the precise assembly of diverse cellular subtypes into neural circuits with species-specific functions. For example, mammals such as bats and dolphins have evolved new senses such as echolocation. Other species have become specialized to rely on a particular sense, such as smell for mice, vision for primates, or touch for blind mole rat species that live underground. How the genetic differences that arise between species produce the remarkable diversity of neural functions that occur in nature remains a fundamental question for evolution, genomics, and neuroscience.

Maybe someday someone can tell us what it’s like to be a bat? Or not.


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