Wiring and Volume Transmission: An Overview of the Dual Modality for Serotonin Neurotransmission

Abstract

Serotonin is a neurotransmitter involved in the modulation of a multitude of physiological and behavioral processes. In spite of the relatively reduced number of serotoninproducing neurons present in the mammalian CNS, a complex long-range projection system provides profuse innervation to the whole brain. Heterogeneity of serotonin receptors, grouped in seven families, and their spatiotemporal expression pattern account for its widespread impact. Although neuronal communication occurs primarily at tiny gaps called synapses, wiring transmission, another mechanism based on extrasynaptic diffusion of neuroactive molecules and referred to as volume transmission, has been described. While wiring transmission is a rapid and specific one-toone modality of communication, volume transmission is a broader and slower mode in which a single element can simultaneously act on several different targets in a one-to-many mode. Some experimental evidence regarding ultrastructural features, extrasynaptic localization of receptors and transporters, and serotonin−glia interactions collected over the past four decades supports the existence of a serotonergic system of a dual modality of neurotransmission, in which wiring and volume transmission coexist. To date, in spite of the radical difference in the two modalities, limited information is available on the way they are coordinated to mediate the specific activities in which serotonin participates. Understanding how wiring and volume transmission modalities contribute to serotonergic neurotransmission is of utmost relevance for the comprehension of serotonin functions in both physiological and pathological conditions.

2-Hydroxy-5-nitro-3-(trifluoromethyl)pyridine as a Novel Matrix for Enhanced MALDI Imaging of Tissue Metabolites

“…Moreover, three other AAs, [histidine + Na] + ( m / z 162.063), [methionine + Na] + ( m / z 172.040), and [3,5-dihydroxyphenylglycine (DHPG) + Na] + ( m / z 206.041), were mainly localized in the Cc, Gp, Ns, Ccx, Hth, and Zi regions. Interestingly, these important AAs are crucial modulatory molecules in the neurotransmitter system, closely associated with neuronal excitation, synaptic plasticity, and regulation of cognitive functions . For instance, methionine was mainly involved in the learning and memory processes in the Hi area and DHPG can inhibit neuronal excitation. , Meanwhile, the ion of [phosphorylcholine + K] + ( m / z 222.028) was approximately observed in the whole brain tissue sections, and this observation was consistent with previous findings .…”

Reversible Morphological Remodeling of Prefrontal and Hippocampal Serotonergic Fibers by Fluoxetine

“…Although no causality was explored here, it is tempting to speculate that the observed morphological effects underlie, at least in part, the therapeutic properties of fluoxetine. Mechanistically, this might involve remodeling not only of the density but also of the types (wiring vs volume transmission) of neurotransmitter-releasing sites, which are known to play relevant and distinct role in serotonergic signaling and most likely modulation of behavioral output . Future studies are needed to test this intriguing hypothesis and shed light on the functions of different serotonergic transmission modalities that are still poorly understood.…”

Modulation of input to the spinal cord; contribution of GABA released by interneurons and glial cells by polarization at the entry of sensory information

“…We consider the reported effects of GABA to be due to its volume transmission Agnati & Fuxe, 2000b;Agnati, 2010;Gianni, 2023) in view of the demonstration of predominant or even exclusively extrasynaptic GABA membrane receptors within the proximal branching regions of afferent fibres, and because the extra-synaptic GABAA receptor antagonist L655708 abolished the sustained effects of epidural polarization (Lucas-Osma et al, 2018;Hari et al, 2022). Within the distal compartments of afferent fibres the relative contribution of GABA modulatory actions evoked via extrasynaptic receptors and via axo-axonal synaptic contacts was concluded to be the opposite, the latter dominating (see in particular Fig.…”