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Each cerebral hemisphere can be divided into three main regions. The outermost region, the cerebral cortex, is a thin layer (2 to 4 millimeters thick) made up of gray matter, consisting of neuron cell bodies, dendrites, glial cells, and blood vessels. The middle region, or white matter, is primarily composed of myelinated nerve fibers organized into three types of large tracts: association fibers, commissures, and projection fibers. Association fibers connect different areas within the same...
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The Enterarchon: An ancient visceral brain.

Bryon Silva1, Mael Lemoine2, Michael Rera3

  • 1Institut du Cerveau-Paris Brain Institute (ICM), Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.

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The ancient gut nervous system, or Enterarchon, predates the brain and regulates homeostasis. This visceral brain integrates signals, challenging brain-centric models of regulation.

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Area of Science:

  • Comparative physiology
  • Neuroscience
  • Evolutionary biology

Background:

  • The gastrointestinal (GI) tract possesses intrinsic and extrinsic neural circuits crucial for digestion, metabolism, and homeostasis.
  • These gut-embedded circuits evolved in parallel across diverse lineages, predating centralized brains.
  • The enteric nervous system (ENS) in vertebrates is well-mapped, while Drosophila offers cellular resolution for linking molecular identity to function.

Purpose of the Study:

  • To explore the evolutionary origins and regulatory roles of the gut-innervating nervous system.
  • To challenge brain-centric models by proposing the gut as a primary homeostatic regulator.
  • To investigate how the intestine-ENS axis integrates signals and undergoes dynamic remodeling.

Main Methods:

  • Comparative analysis across metazoans, from early-diverging animals to Drosophila and vertebrates.
  • Leveraging Drosophila models for high-resolution cellular and functional studies.
  • Integrating data on neuronal, epithelial, and immune components of the intestine-ENS axis.

Main Results:

  • Gut-embedded circuits evolved early, coordinating motility and secretion before centralized brains.
  • The intestine-ENS axis integrates endocrine and immune signals.
  • The gut undergoes remodeling influenced by sex, reproduction, and aging.

Conclusions:

  • The intestine, through its integrated components, functions as an "Enterarchon"—an ancient visceral brain.
  • This Enterarchon plays a fundamental role in shaping organismal homeostasis.
  • A gut-centric view is proposed to complement or challenge traditional brain-centric models of systemic regulation.