Synaptic versus non-synaptic neurotransmission E. Sylvester Vizi, Balázs Lendvai, Balázs Rózsa Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Tamás Roska Computer and Automation Research Institute, Hungarian Academy of Sciences, Budapest, Hungary

It is generally accepted that information is conveyed chemically from one nerve terminal to another neuron (cell body or terminal), in which the transmitter is stored in vesicles and released into the synaptic gap in quanta. This system is adopted for very fast signalling. The information transfer is within millisecond time intervals and is able to transmit messages of several hundred action potentials per second (10-200 Hz).

This synaptic arrangement e.g. instantiated within the dendrite provides a functional scaffold over which to conduct neuronal computation. The efficacy of inhibitory or excitatory inputs appears to be locally restricted and critically dependent on their spatial and temporal proximity to excitatory or inhibitory inputs (on the same dendritic branch). The few milliseconds of membrane depolarization or hyperpolarization over a time window might not contain as much information for representation of overall synaptic inputs as do continuous subthreshold non-synaptic inputs resulting in a longlasting depolarization or hyperpolarization.

Neurochemical (Vizi, 1984, 2000; cf. Kiss and Vizi, 2001) and morphological  evidence has shown that some neurotransmitters may be released from nonsynaptic sites into the extracellular space(~20% of human brain volume) for diffusion to target cells more distant (~ few hundred µm) than those observed in synaptic transmission. These findings indicate that there is functional interaction (presynaptic inhibition) between neurons without any morphological contact (cf. Vizi, 1980a, 1984a). The nonsynaptic interactions between neurons would be a form of communication transitional between discrete classic neurotransmission (in Sherrington’s synapse) and the relatively nonspecific neuroendocrine secretion. The majority of noradrenergic, dopaminergic and serotonergic varicosities in the CNS does not make synaptic contacts. Recent findings indicate that in addition to these endogenous ligands (norepinephrine, dopamine, and serotonin), other transmitters, such as nitric oxide (NO), also may be involved in these nonsynaptic interactions. NO can influence the function of uptake carrier systems, which may be an important factor in the regulation of extracellular concentration of different transmitters. Recent immunoelectromicroscipic studies have revealed a low incidence (14% in cerebral cortex, 7% in the hippocampus, < 10% olfactory bulbs, and 9% in he striatum) of synaptic specializations of cholinergic varicosities. This fact indicates, that acetylcholine can act extrasynaptically. In addition there is convincing evidence that neurons are able to release transmitter whose release is not coupled to action potential. E.g. during ischemia the release due to axonal stimulation is completely inhibited, but there is a huge release due to reverse operation of the transporter.

It seems that int he brain beside synaptic (digital) signal transmission there is a nonsynaptic (analog) communication system.

Recommended publications:

Vizi, E.S. Physiological role of cytoplasmic and non-synaptic release of transmitter. Neurochem.Int. 6:435-440 (1984)

Vizi, E.S.  Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in the CNS.  Pharmacol. Rev. 52:63-89 (2000)

Kiss, J.P. and Vizi, E.S.  Nitric oxide: A novel link between synaptic and nonsynaptic transmission.  Trends Neurosci. 24: 211-215 (2001).