Volume transmission and its different forms in the central nervous system

Abstract

Volume transmission (VT) is a widespread mode of intercellular communication that occurs in the extracellular fluid (ECF) and in the cerebrospinal fluid (CSF) of the brain with VT signals moving from source to target cells via energy gradients leading to diffusion and convection (flow). The VT channels are diffuse forming a plexus in the extracellular space, while in wiring transmission (WT) the channels (axons, terminals) are private. The speed is slow (seconds-minutes) in VT while rapid in the millisecond range in WT. The extracellular space is the substrate for VT, which is modulated by the extracellular matrix. Extrasynaptic VT is linked to synaptic transmission and likely often takes place due to incomplete diffusion barriers with the synaptic transmitter reaching extrasynaptic domains of the pre-and post-synaptic membrane of the synapse, the astroglia, and even adjacent synapses. Indications exist for the existence of striatal D2-like receptor-mediated extrasynaptic form of dopamine (DA) VT at the local circuit level in vivo in the human striatum. Synaptic glutamate via extrasynaptic VT can act on extrasynaptic metabotropic glutamate receptors located on the astroglia leading to Ca(2+) mediated astrocytic glutamate release into the extracellular space (ECS). Long distance peptide VT and CSF VT is the major long distance VT with distances more than 1 mm and flow in the CSF. Indications for long distance VT of beta-endorphin and oxytocin are obtained. We propose that monogamy in the female prairie vole may take place through an increase in oxytocin VT, especially in nucleus accumbens. Release of extracellular vesicles containing receptors, proteins, RNAs and mtDNA from cellular networks in the central nervous system (CNS) into the ECF and CSF may be a fundamental communication in the CNS. It represents a special form of volume transmission, the Roamer subtype of VT. It may greatly contribute to dynamic events of synaptic plasticity but also to spread of pathological proteins in protein conformational disorders. VT also occurs in the peripheral nervous system and associated cells. Short and long distance VT may take place in meridian channels via diffusion and flow in the interstitial fluid. Acupuncture can produce VT signals by releasing transmitters and modulators from nerve terminals and mast cells.

Hypocretin1/orexinA-immunoreactive axons form few synaptic contacts on rat ventral tegmental area neurons that project to the medial prefrontal cortex

“…Thus, Hcrt1/OxA could affect VTA function synaptically, but also perhaps through non-synaptic actions that have been reported typical of peptidergic transmission [24, 25]. Here we hypothesize that some of those neurons targeted by Hcrt1/OxA axons belong to the mesocortical pathway.…”

Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress

“…In contrast, to modulate brain functions, the action of blood‐borne peripheral messengers, such as peptide hormones and lipids, is specified by their ability to cross the blood–brain barrier and the cell‐type specificity of their cognate receptors (Alpár & Harkany, 2013). An intermediary between these mechanisms is volume transmission, defined as a lack of specific and spatially demarcated conduits between the site of ligand production and receptor‐mediated signaling within a specific tissue (Fuxe et al , 2013). Purines and purine nucleotides (e.g., ATP), catecholamines, and hormones are commonly used for both short‐ and long‐range volume transmission (Fuxe et al , 1988; Roper, 2007; Housley et al , 2009).…”

On the role of adenosine (A)2A receptors in cocaine-induced reward: a pharmacological and neurochemical analysis in rats

“…This interaction inter alia occurs in the ventral striato-pallidal GABA pathway ) which executes expression of rewarding/motivational/seeking properties of cocaine or food (Di Chiara 1995;Sizemore et al 2000;Tang et al 2005;Wydra et al 2013). The enhancing actions of cocaine on D 2 receptor signaling involve also indirect DA releasing actions and direct effects on D 2 receptor signaling in D 2 homo or heteroreceptor complexes like the A 2A -D 2 heteroreceptor complexes Filip et al 2012;Fuxe et al 2013) which leads to enhancement of D 2 -mediated DA neurotransmission.…”