Neurotransmitters before neurons
Neurotransmitters and their receptors are used by tissues that have no neurons. In the held texts, serotonin is the main example. Levin and colleagues report that it acts in embryonic patterning and regeneration, moved by voltage and through gap junctions.13 They argue that the molecular tools of the brain are expressed throughout the body, so these molecules have roles outside the nervous system.4
- Earliest held
- 2010, Blackiston D, Shomrat T…
- Most discussed in
- The Computational Boundary of a "Self"…, 2019
- In the library
- 156 passages in 45 works
- Rewritten
- 2026-10-03
Serotonin in the embryo
Carneiro and colleagues (2011) describe a model of left-right patterning that focuses on stages before gastrulation. In it, the chirality of the cytoskeleton sets up asymmetric movement of morphogens through fields of cells. Serotonin (5HT) is one such morphogen. In chick and frog, serotonergic signaling is required for left-right patterning. In the frog embryo, 5HT accumulates in the right blastomeres. The process is rapid and depends on voltage gradients across the midline and on open gap junctions.1 Levin (2022) credits Fukumoto and colleagues (2005) with the discovery of pre-neural roles for serotonin, and counts it among the fruits of a view of anatomical homeostasis as collective intelligence.7
Planarian regeneration
Durant and colleagues (2016) review work on planarians. They note that neurotransmitters and receptors are widely present in flatworms and that earlier surveys found many effects of neurotransmitter modulation on regeneration. Praziquantel, a drug that raises the permeability of the tegument to calcium, induced bipolar worms (Chan et al. 2014). Exogenous serotonin rescued this effect (Chan et al. 2015).2 Pietak and colleagues (2019) built a model of axis control. They report that its results on cAMP fit a role for cAMP downstream of an abundantly expressed 5HT7-like serotonin receptor.5
Feedback with gap junctions
Durant and colleagues note that serotonin both regulates gap junctional communication and passes through gap junctions as a morphogen. They suggest this allows feedback loops with rich behavior. They propose that the voltage-serotonin cycle may work beyond the central nervous system, as a second messenger pathway for bioelectric control of intracellular events.3 Levin (2023) describes the same coupling. Bioelectric states move neurotransmitters such as serotonin through the extracellular space and directly through gap junctions. His conceptual table maps neuromodulation onto developmental, pre-nervous signaling by serotonin under bioelectric control.8
Beyond animals with embryos
Baluška and Levin (2016) state that gap junctions, ion channels and neurotransmitter pathway molecules are broadly expressed through the body, starting before fertilization. They add that non-neural tissues regulate resting potential in a way that is analogous to the brain.4 Levin (2019) points to the use of neurotransmitters downstream of bioelectric forces, citing GABA and the serotonin-like auxin in many plants.6 Xiang and colleagues (2023) add a complication from sponges. The sponge genome lacks a gene for aromatic L-amino acid decarboxylase. Serotonin in sponges appears to be made by bacterial symbionts, not by the host.9
In the frog embryo, it is known that 5HT accumulates in the right blastomeres in a rapid process dependent on asymmetric voltage gradients across the midline
Carneiro K, Donnet C, Rejtar T, Karger BL, Barisone GA…, 2011 · Histone deacetylase activity is necessary for left-right patterning during… · open at passage 5induced bipolar phenotypes in planaria (Chan et al. 2014) and can be rescued with exogenous serotonin (Chan et al. 2015).
Durant F, Lobo D, Hammelman J, Levin M, 2016 · Physiological controls of large-scale patterning in planarian regeneration: a… · open at passage 17serotonin has been shown to regulate gap junctional communication (GJC) (Rorig & Sutor 1996; Orellana et al. 2013) whilst also being a GJ permeable morphogen (Levin 2006; Gairhe et al. 2012)
Durant F, Lobo D, Hammelman J, Levin M, 2016 · Physiological controls of large-scale patterning in planarian regeneration: a… · open at passage 18are broadly expressed throughout the body, beginning prior to fertilization. Analogously to the brain, non-neural tissues continuously regulate resting potential (Vmem)
Baluška F, Levin M, 2016 · On Having No Head: Cognition throughout Biological Systems · open at passage 43corroborates the previously suggested role for cAMP acting downstream of G-protein coupled receptor (GPCR) signaling through an abundantly-expressed 5HT7-like serotonin receptor [42].
Pietak A, Bischof J, LaPalme J, Morokuma J, Levin M, 2019 · Neural control of body-plan axis in regenerating planaria · open at passage 60the ubiquitous use of neurotransmitter molecules downstream of bioelectric driving forces [e.g., GABA and the serotonin-like Auxin used in many plants (Ramesh et al., 2015)].
Levin M, 2019 · The Computational Boundary of a "Self": Developmental Bioelectricity Drives… · open at passage 48It led to the discovery of reprogrammable head number in planaria (Nogi and Levin, 2005) and of pre-neural roles for serotonin (Fukumoto et al., 2005a,b).
Levin M, 2022 · Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework… · open at passage 66Developmental (pre-nervous) signaling via neurotransmitters such as serotonin moving under control of bioelectrical gradients
Levin M, 2023 · Bioelectric networks: the cognitive glue enabling evolutionary scaling from… · open at passage 23Another neurotransmitter detected in sponges, serotonin, also appears to be produced by bacterial symbionts (Hedner et al., 2006; Leys, 2015).
Xiang X, Vilar Gomez AA, Blomberg SP, Yuan H, Degnan BM…, 2023 · Potential for host-symbiont communication via neurotransmitters and… · open at passage 27