Difference between revisions of "Draft:Two Forms of Electrical Transmission Between Neurons"

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<br />Donald S. Faber^1,2 and Alberto E. Pereda^1,2*

==Two Forms of Electrical Transmission Between Neurons==

===Introduction===

===The Search for the Mechanisms of Synaptic Transmission===

===Synaptic Transmission Mediated by Pathways of Low Resistance: Gap Junctions===

Rather than simple conduits the gap junction channels themselves contribute to electrical communication. The molecular composition and properties of the gap junction intercellular channel have been shown to endow electrical transmission with voltage-dependent properties. Hemichannels that contribute to form the intercellular channel can be made of the same or different connexin or innexin proteins. Intercellular channels formed by hemichannels made of the same protein are called “homotypic,” whereas channels formed by hemichannels made of different proteins are called “heterotypic” ​(Figure3A, inset). Molecular differences between the involved hemichannels are commonly associated with rectification of electrical transmission (Barrio et al., 1991; Verselis et al., 1994) and, providing support for such prediction, this association has been observed for both connexin (Rash et al., 2013) and innexin-based electrical synapses (Phelan et al., 2008). Rectification refers to the ability of electrical currents to preferentially flow in one direction, in other words, they behave as electrical diodes. However, this property critically depends on the polarity of the signal. As observed in the crayfish giant fiber synapses (Furshpan and Potter, 1959; Giaume et al., 1987), depolarizations can travel from the presynaptic to the postsynaptic side but not in the opposite directions, and hyperpolarizations can travel from the postsynaptic to the presynaptic side but not the other direction ​(Figure3C). The polarized features of electrical transmission suggest the existence of a voltage-sensitive mechanism underlying this property. Several mechanisms were proposed to contribute to steep electrical rectification of gap junction channels, such as that observed in crayfish. Electrical rectification can be a consequence of the separation of fixed positive and negative charges at opposite ends of heterotypic gap junction channels, configuring a “p-n junction,” which results from asymmetries in the molecular composition of the hemichannels that form the intercellular channel (Oh et al., 1999). Alternatively, electrical rectification could result from the presence of charged cytosolic factors which alter channel conductance, such as Mg++ (Palacios-Prado et al., 2013, 2014) and spermine (Musa et al., 2004), which were to shown to interact with the gap junction channel. Combinations of these or more factors are likely to contribute to this striking voltage-dependent feature of some electrical synapses (reviewed in Palacios-Prado et al., 2014). Finally, the conductance of neuronal gap junctions was shown to be target of numerous regulatory mechanisms that endow electrical synapses with plastic properties equivalent to those observed at chemical synapses (reviewed in Pereda et al., 2013; O’Brien, 2014, 2017; Pereda, 2014).

===Synaptic Transmission Mediated by Electric Fields===

The Mauthner cell is a large identifiable midbrain neuron found in many teleosts, and it has a number of morphological specializations that make it an unique model system. Furukawa and Furshpan (1963) discovered the first example of electrical inhibition when comparing the intra- and extracellular potentials evoked in the axon cap by antidromic stimulation of this neuron’s axon—as noted, the axon cap is a dense neuropil surrounding the initial segment of the Mauthner cell axon. First, the antidromic action potential in the extracellular space (Ve) is very large and negative, as much as −40 mV, and the corresponding spike height recorded intra-axonally (Vi) at the site of spike initiation is smaller, ~+50 mV, so that the full transmembrane spike height, calculated as the difference between the intra- and extracellular responses, i.e., Vi − Ve, ~+90 mv (Furshpan and Furukawa, 1962). This observation of such a large extracellular potential associated with one neuron’s action potential suggested a high resistance barrier to extracellular current, and it has been proposed that this property is a consequence of the structure of the axon cap: swelling of interneuron axons at the edge of the cap, and close proximity to a densely packed ring of glia at the same boundary, known as the “canestro” or “basket” of Beccari (1907). These morphological features represent cellular specializations that support electrical communication and, therefore, may be analogous to structural specializations found at chemical synapses. Furthermore, the antidromic spike was succeeded by an extracellular positivity, which they named the Extrinsic Hyperpolarizing Potential (EHP) since it was larger than its intracellular representation, and, thus the same calculation showed that (Vi - Ve) < 0 and that the EHP is inhibitory. It was shown subsequently that the EHP was generated by impulses in a class of inhibitory interneurons that mediate feedback and feedforward inhibition of the Mauthner cell and that the evoked inhibition has two components, with a classical glycinergic inhibition of the Mauthner cell following the electrical component by ~0.5 ms (Figure 4A; Korn and Faber, 1976). In the case of the feedforward circuit, the short latency allows electrical inhibition to occur synchronously with excitation, thereby limiting the duration of the decision-making window in processing information by the Mauthner cell. Thus, these connections mediate mixed, electrical and chemical, synaptic actions ​(Figure 4A).

===Summary===

==Bibliography==