New concepts of molecular communication among neurons

Abstract

Recently a number of complex electrophysiological responses to neurotransmitters have been observed that cannot be described as simple excitation or inhibition. These responses are often characterized as modulatory, although there is no consensus on what defines modulation. Morphological studies reveal certain neurotransmitters stored in what might be release sites without synaptic contact. There is no direct evidence for nonsynaptic release from CNS sites, although such release does occur in the periphery and in invertebrates. Nonsynaptic release might provide a basis for diffuse one-cell-to-many communication, but it might also simply be a means of sending the transmitter to a broader area of a single neuron than occurs in typical synapses. Several kinds of macromolecules have been found to be transported in a retrograde direction – and in some cases transsynaptically. There have been suggestions that some neurons may release more than one type of transmitter. Particularly intriguing is the possibility of release of substances that modulate actions of a primary transmitter. Taken together this range of evidence suggests that neurons may use a variety of forms of molecular communication in addition to traditionally described synaptic transmission.Several authors have suggested modes of communication distinct from classical synaptic transmission and have classified released substances using terms such as neurohumor, neurohormone, neuroregulator, and modulator. These suggestions have the heuristic value of drawing together diverse kinds of data, but it remains to be established that the pieces fit together in that fashion – for example, that complex electrophysiological effects are associated with substances released nonsynaptically. In order to reduce confusion, a flexible, generic approach to nomenclature for substances released from neurons and for hypothetical modes of communication is recommended. Some behavioral implications of nonconventional transmission are considered.

Statistical mechanics of neocortical interactions: A scaling paradigm applied to electroencephalography

“…These long-ranged interactions are also important for collective activity in the mammalian cortex [45], and they are included in this study. Longer-time, weaker and modulatory nonsynaptic influences arising from humoral and electrotonic interactions [73][74][75] are included, only as their averaged properties affect synaptic parameters.…”

Pericapillary and distant axon terminals in the nuclei of the cat amygdala: a morphometric study

“…The existence of asynaptic axon terminals in the CNS, predominantly catecholaminergic, was described by Beaudet and Descarries (1978), Dismukes (1979), Pickel (1986), Maley et al (1990), Aoki and Pickel (1992), Bach-y-Rita (1993), and Benes et al (1993). Transmission without structurally apparent membrane specialization may also take place between a nerve terminal and a capillary vessel wall (Rennels and Nelson 1975;Swanson el al.…”

Membrane mechanism of neuroendocrine caudo‐dorsal cell inhibition by the ring neuron in the pond snail Lymnaea stagnalis

“…This would explain the variation in latency reported here. When these assumptions turn out to be true, we may thus be dealing with a good example of nonsynaptic transmission within the central nervous system of Lymnaea (Dismukes, 1979). The RN itself receives a number of inputs: It is excited by a local action of the CDC, inhibited by a factor released into the blood by the CDCs, and it receives large epsps on electrical penis nerve stimulation.…”