Cellular basis of brain maturation and acquisition of complex behaviors in salamanders

Abstract

The overall bauplan of the tetrapod brain is highly conserved, yet significant variations exist among species in terms of brain size, structural composition and cellular diversity. Understanding processes underlying neural and behavioral development in a wide range of species is important both from an evolutionary developmental perspective as well as for the identification of cell sources with post-developmental neurogenic potential. Here, we characterize germinal processes in the brain of and during both development and adulthood. Using a combination of cell tracking tools, including clonal analyses in new transgenic salamander lines, we examine the origin of neural stem and progenitor cells found in the adult brain, determine regional variability in cell cycle length of progenitor cells, and show spatiotemporally orchestrated neurogenesis. We analyze how maturation of different brain regions and neuronal subpopulations are linked to the acquisition of complex behaviors, and how these behaviors are altered upon chemical ablation of dopamine neurons. Our data analyzed from an evolutionary perspective reveal both common and species-specific processes in tetrapod brain formation and function.

Walking with Salamanders: From Molecules to Biorobotics

“…It has also become routine to carry out systematic gene perturbation studies during both salamander development and regeneration. In the CNS specifically, cell proliferation and migration could be assessed during brain development at clonal resolution (e.g., [63]). Inducible Cre recombinase has been knocked into gene loci to trace cells and to mutate specifically targeted genes during spinal cord regeneration using CRISPR/Cas9-mediated technology (e.g., [64,65]).…”

“…At the cellular level, the putative circuitry underlying gait transition was explored using a brainstem-spinal cord network built with three-compartment Hodgkin and Huxley model neurons with >10 conductances [95]. A single synapse from excitatory neurons of the limb circuit to the swimming circuit was sufficient to recapitulate the switch between walking and swimming [63]). (G-J) Imperfect rewiring of the CNS in animals that recovered locomotion after a complete SCI.…”

A Comparative Perspective on Brain Regeneration in Amphibians and Teleost Fish

“…In contrast to the axolotl, homeostatic proliferation in the red spotted newt is restricted to the forebrain, but quiescent ependymoglia cells can also proliferate in response to injury and regenerate lost cell types in other brain regions such as the midbrain (Berg et al , ). Ependymoglia have been identified as the source of brain regeneration in both the red spotted and Iberian newts, through thymidine analogue incorporation and lineage tracing by electroporation of reporter constructs (Berg et al , ; Kirkham et al , ; Joven et al , )., Two types of ependymoglia have been identified in the telencephalon of the red spotted newt, and these are distributed unevenly along the ventricle (Kirkham et al , ). Type‐1 ependymoglia are dispersed along the ventricle and create new neurogenic regions after injury.…”

“…Furthermore, the three currently most widely used species, the red spotted newt, the Iberian ribbed newt ( Pleurodeles waltl ), and the axolotl, exhibit clear differences in the proliferation pattern of brain ventricular cells. The proliferation of these cells ranges from complete quiescence to continuous proliferation, which offers an attractive base for comparative studies (Berg et al , ; Maden et al , ; Joven et al , ). Recent efforts in sequencing the genomes of Xenopus laevis (Session et al , ), axolotl (Nowoshilow et al , ), and the Iberian ribbed newt (Elewa et al , ) as well as the establishment of genetic tools, such as lineage tracing (Khattak et al , ; Joven et al , ) and CRISPR/Cas9‐mediated genome editing (Blitz et al , ; Fei et al ., ; Aslan et al , ; Elewa et al , ) provide new opportunities to study brain regeneration in exquisite detail in these animals (Table ).…”

Patch-clamp recordings in slices of telencephalon, diencephalon and rhombencephalon of salamanders

“…They are the closest representative of the first tetrapods, therefore allowing researchers to infer the evolution of the locomotor circuitry during the transition to land (Ijspeert et al 2007). They regenerate their spinal cord after a complete transection (Chevallier et al 2004) or after major destruction of their brain dopaminergic system (Joven et al 2018), providing a unique opportunity to dissect the reconnection maps leading to functional recovery in limbed vertebrates.…”