Transcriptomic evidence for dense peptidergic networks within forebrains of four widely divergent tetrapods

The primary function common to every neuron is communication with other neurons. Such cell–cell signaling can take numerous forms, including fast synaptic transmission and slower neuromodulation via secreted messengers, such as neuropeptides, dopamine, and many other diffusible small molecules. Individual neurons are quite diverse, however, in all particulars of both synaptic and neuromodulatory communication. Neuron classification schemes have therefore proven very useful in exploring the emergence of network function, behavior, and cognition from the communication functions of individual neurons. Recently published single-cell mRNA sequencing data and corresponding transcriptomic neuron classifications from turtle, songbird, mouse, and human provide evidence for a long evolutionary history and adaptive significance of localized peptidergic signaling. Across all four species, sets of at least twenty orthologous cognate pairs of neuropeptide precursor protein and receptor genes are expressed in individually sparse but heavily overlapping patterns suggesting that all forebrain neuron types are densely interconnected by local peptidergic signals.