ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2021
The chemical brain hypothesis for the origin of nervous systems.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 108 citations in OpenAlex.
- Revisiting nerve nets: functional organization and evolutionary implications.The EMBO journal · 2026Review
- Behaviour without synapses: peptidergic signalling as a mode of behavioural coordination.Nature reviews. Neuroscience · 2026Article
- Neuropeptides in control of left-right neural circuits.Trends in neurosciences · 2026Review
- The evolutionary origins of synaptic proteins and their changing roles in different organisms across evolution.Nature reviews. Neuroscience · 2026Review
- Chemical multiplexing in the nervous system: molecular architecture, functional stratification, and pathophysiological plasticity of neuropeptide-classical neurotransmitter cotransmission.Frontiers in molecular neuroscience · 2026Review
- Smell Is Emotion.Brain sciences · 2025Article
- Early transitions in the evolution of cognition.History and philosophy of the life sciences · 2025Article
- Four neurons pattern brain-wide developmental activity through neuropeptide signaling.bioRxiv : the preprint server for biology · 2025Article
- Innovations in spinal cord cell type heterogeneity across vertebrate evolution.bioRxiv : the preprint server for biology · 2025Article
- Beyond synapses: cytoplasmic connections in brain function and evolution.Biological reviews of the Cambridge Philosophical Society · 2025Review
- AnOpen biology · 2025Article
- Molecular mimicry: ecology, evolution, and applications of doppelgänger peptides.Trends in biochemical sciences · 2025Review
- A Call for Conceptual Clarity: "Emotion" as an Umbrella Term Did Not Work-Let's Narrow It Down.Brain sciences · 2025Review
- An AlphaFold guided model for the evolution of the CaMKII interactome.bioRxiv : the preprint server for biology · 2025Article
- Divergence in neuronal signaling pathways despite conserved neuronal identity among Caenorhabditis species.Current biology : CB · 2025Article
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- Neuropeptide signaling network of Caenorhabditis elegans: from structure to behavior.Genetics · 2024Review
- Fundamental constraints to the logic of living systems.Interface focus · 2024Review
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- Dynamics of neural activity in early nervous system evolution.Current opinion in behavioral sciences · 2024Article
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1 author at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
In nervous systems, there are two main modes of transmission for the propagation of activity between cells. Synaptic transmission relies on close contact at chemical or electrical synapses while volume transmission is mediated by diffusible chemical signals and does not require direct contact. It is possible to wire complex neuronal networks by both chemical and synaptic transmission. Both types of networks are ubiquitous in nervous systems, leading to the question which of the two appeared first in evolution. This paper explores a scenario where chemically organized cellular networks appeared before synapses in evolution, a possibility supported by the presence of complex peptidergic signalling in all animals except sponges. Small peptides are ideally suited to link up cells into chemical networks. They have unlimited diversity, high diffusivity and high copy numbers derived from repetitive precursors. But chemical signalling is diffusion limited and becomes inefficient in larger bodies. To overcome this, peptidergic cells may have developed projections and formed synaptically connected networks tiling body surfaces and displaying synchronized activity with pulsatile peptide release. The advent of circulatory systems and neurohemal organs further reduced the constraint imposed on chemical signalling by diffusion. This could have contributed to the explosive radiation of peptidergic signalling systems in stem bilaterians. Neurosecretory centres in extant nervous systems are still predominantly chemically wired and coexist with the synaptic brain. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.
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