Axon terminals always form synapses rather than releasing neurotransmitters into the extracellular space
Axon terminals do not exclusively form classical synapses; many release neurotransmitters directly into the extracellular space to engage in volume or extrasynaptic transmission.
The claim states that axon terminals *always* form synapses rather than releasing neurotransmitters into the extracellular space. Multiple papers ([0], [1], [2], [4], [8]) directly refute this by demonstrating the existence and physiological significance of non-synaptic terminals and volume transmission (extrasynaptic diffusion of neurotransmitters).
B. Bjelke, M. Goldstein, B. Tinner, C. Andersson, S. Sesack, H. Steinbusch, J. Lew, Xi C. He, S. Watson, B. Tengroth, K. Fuxe. Dopaminergic transmission in the rat retina: evidence for volume transmission.. 1996. https://doi.org/10.1016/S0891-0618(96)00176-7
Demonstrates that dopaminergic transmission in the retina operates via volume transmission by releasing neurotransmitters into the extracellular space where they diffuse to distant receptors.
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Charles Ducrot, Marie-Josée Bourque, Constantin V. L. Delmas, Anne-Sophie Racine, Dainelys Guadarrama Bello, Benoît Delignat-Lavaud, M. D. Lycas, Aurélie Fallon, Charlotte Michaud-Tardif, Samuel Burke, Freja Herborg, U. Gether, A. Nanci, Hideto Takahashi, M. Parent, L. Trudeau. Dopaminergic neurons establish a distinctive axonal arbor with a majority of non-synaptic terminals. 2020. https://doi.org/10.1096/fj.202100201RR
Shows that monoamine neurons, such as dopaminergic neurons, establish a majority of non-synaptic terminals that release neurotransmitters without forming classical synapses.
Gianni G, Pasqualetti M. Wiring and Volume Transmission: An Overview of the Dual Modality for Serotonin Neurotransmission.. 2023. https://doi.org/10.1021/acschemneuro.3c00648
Discusses volume transmission as a dual modality where neuroactive molecules undergo extrasynaptic diffusion rather than point-to-point wiring transmission.
Miklós Antal. Molecular Anatomy of Synaptic and Extrasynaptic Neurotransmission Between Nociceptive Primary Afferents and Spinal Dorsal Horn Neurons. 2025. https://doi.org/10.3390/ijms26052356
Reports that certain molecules like neuropeptides are released extrasynaptically to modulate neuronal function via volume transmission rather than forming direct synaptic contacts.
Paul Bach-y-Rita. Nonsynaptic Diffusion Neurotransmission and Brain Plasticity. 1996. https://doi.org/10.1177/107385849600200511
Explains nonsynaptic diffusion neurotransmission, where neurotransmitters diffuse through the extracellular fluid from remote release points to activate extrasynaptic receptors.
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