Function and Plasticity of Electrical Synapses in the Mammalian Brain: Role of Non-Junctional Mechanisms

SIMPLE SUMMARY: Relevant brain functions, such as perception, organization of behavior, and cognitive processes, are the outcome of information processing by neural circuits. Within these circuits, communication between neurons mainly relies on two modalities of synaptic transmission: chemical and electrical. Moreover, changes in the strength of these connections, aka synaptic plasticity, are believed to underlie processes of learning and memory, and its dysfunction has been suggested to underlie a variety of neurological disorders. While the relevance of chemical transmission and its plastic changes are known in great detail, analogous mechanisms and functional impact of their electrical counterparts were only recently acknowledged. In this article, we review the basic physical principles behind electrical transmission between neurons, the plethora of functional operations supported by this modality of neuron-to-neuron communication, as well as the basic principles of plasticity at these synapses. ABSTRACT: Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals, they are mostly composed of the protein connexin36. Circuits of electrically coupled neurons are widespread in these animals. Plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations such as lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on the gap junction resistance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage and ligand gated channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here, we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.