Functional Sensory Circuits Built from Neurons of Two Species

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2024 Apr 26

PMID 38670072

Authors

Benjamin T Throesch

Muhammad Khadeesh Bin Imtiaz

Rodrigo Munoz-Castaneda

Masahiro Sakurai

Andrea L Hartzell

Kiely N James

Alberto R Rodriguez

Greg Martin

Giordano Lippi

Sergey Kupriyanov

Zhuhao Wu

Pavel Osten

Juan Carlos Izpisua Belmonte

Jun Wu

Kristin K Baldwin

Affiliations

Soon will be listed here.

Abstract

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.

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