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Gap junctions are an evolutionarily ancient form of intercellular communication, present in a variety of tissues, and essential to life. A variety of types of experimental evidence indicates that gap junctions can occur on axons, and can (at least in some circumstances) permit the spread of action potentials from cell to cell. Very fast oscillations at ~200 Hz occur in hippocampal slices in conditions where chemical synapses are blocked, but requiring gap junctions.

This chapter focuses on gap junctions and “half” gap junctions called hemichannels. The channels comprising a gap junction are large-diameter aqueous pores that extend from one cell, across the extracellular space, into an adjacent cell. These channels allow all inorganic ions and small organic molecules to diffuse freely from the interior of one cell into the interior of another cell. The general features of gap junctions and gap junctions in glial cells are discussed.

VFO occurs in in vitro models when chemical receptors are blocked. In particular, VFO does not require GABA_A receptors, even though interneurons fire at high rates during in vivo very fast oscillations. VFO can be accounted for by a model in which neuronal spiking percolates through a sparse network of electrically coupled axons. This model predicts that VFO frequency depends on gap junction conductance, mediated by an effect on crossing time (i.e. the time it takes for a spike in one axon to elicit a spike in a coupled axon, estimated to be of order 0.2 ms). VFO in cerebellar slices also depends on gap junctions, but the physical principles are slightly different: cerebellar VFO appears to depend on many:one propagation of spiking, in effect a form of axonal coincidence detection.

Gamma oscillations can be elicited in hippocampal and neocortical slices, by carbachol and by kainate. Pyramidal neurons fire at low rates, but fast-spiking interneurons fire at near gamma rates. The oscillations require gap junctions, presumably on axons, as the oscillations are still present in a connexin36 knockout (although at reduced power). In a model that accounts for this type of gamma, brief bursts of VFO are generated by the plexus of pyramidal cell axons, that are electrically coupled with one another. This VFO synaptically forces interneurons to fire, and feedback inhibition shuts off the VFO. Neocortical gamma, in at least some regions of cortex, appears to depend on chattering cells as well, but not in the expected fashion (i.e. not as a result of the synaptic output of the chattering cells).

Neuromodulatory substances evoke beta2 oscillations in motor and secondary somatosensory cortex, that depend on gap junctions. In the latter case, the oscillations are only weakly dependent on synaptic transmission. Beta2 is most prominent in intrinsically bursting layer 5 pyramidal cells (some of which are expected to contribute to the pyramidal tract, at least in primates). The oscillation is an emergent phenomenon, in that individual neurons are not oscillators at beta2 frequency. The period is determined in part by the “M” type of K⁺ current. Oscillations in deep and superficial cortical layers interact with one another. Gap junctions mediating beta2 are probably located on axons.

Epilepsy can be viewed from inter-related clinical and electrical/cellular points of view. Before and during a so-called electrographic seizure, neuronal events become both highly correlated (synchronized) and also organized in time. The latter organization occurs over a wide range of frequencies. Prior to seizures, very fast oscillations (VFO, >70-80 Hz) occur, that are dependent on gap junctions. Understanding how VFO is generated may provide a therapeutic target.

Disease processes affecting the cerebellum and its connections, such as can occur in multiple sclerosis, often lead to lack of motor coordination, postural tremor, and tremor on directed movement; these symptoms can be difficult to treat. The cerebellum generates oscillations over a range of frequencies (beta, gamma, very fast) and some of these are coherent with oscillations in thalamus and in muscle. Genetically modified ataxic mice can exhibit short runs of very fast oscillations that are gap junction dependent. Oscillations can also be induced in cerebellar cortex slices: gamma and very fast oscillations both require gap junctions, and gamma also depends on synaptic inhibition.

Recent advances in cellular physiological techniques, particularly the development of in situ whole-cell patch-clamp recording, have permitted detailed physiological and pharmacological studies of proliferating cells in the ventricular and subventricular zones of embryonic neocortex. The results are beginning to shed light on the kinds of signals and cellular interactions that may underlie the regulation of cell-cycle events and gene expression in cortical progenitor cells. This chapter discusses the following topics: gap-junction channels provide an avenue for intracellular communication among cortical progenitors; uncoupling blocks DNA synthesis; the principal excitatory and inhibitory amino acid receptors are expressed before neuronal differentiation; cell-cycle events in the embryonic cortex are influenced by GABA and glutamate; GABA depolarizes ventricular zone cells because of high intracellular chloride concentration maintained by a chloride exchange pump; depolarization mediates the DNA synthesis inhibition induced by GABA and glutamate.

The Neuralia (Cnidaria + Ctenophora + Bilateria) is a clade whose most conspicuous apomorphy is the presence of specialised communication cells, neurons with axons, electrical synapses known as gap junctions, chemical synapses with various neurotransmitters, and signal propagation via action potentials using sodium ion/potassium ion channels. The neuralians also possess special sensory cells and special muscle cells. Trichoplax has contractile elements in the inner syncytial meshwork, but lacks special nervous, sensory, or muscle cells.

This chapter discusses some of the basic features of neuronal circuits underlying the population rhythms that can be generated in very small areas of the cortex from slow waves up to extremely fast oscillations. These rhythms are produced via intrinsic neuronal properties combined with chemical and electrical synaptic connectivity profiles. Multiple concurrently generated cortical rhythms can exhibit various forms of coordination, such as concatenation. After providing an overview of how rhythms are generated in the cortex, the chapter examines features of local cortical circuits that generate rhythms. It also discusses synaptic excitation and synaptic inhibition, gap junctions, and features involved in dynamic coordination in the brain.