Synapses and Gap Junctions

Synapses are electrical or chemical communicative contacts between neurons. Electrical synapses (neuronal gap junctions) function by the propagation of electrical impulses from one cell to another (and vice versa) via direct, physical contact. As a consequence, these synapses are characterized by a relatively simple organization of membrane structure and associated organelles (Zoidl et al. 2002). Electrical synapses are also less mutable, in terms of their function and molecular characteristics, and thus exhibit little of the plasticity that typifies the chemical synapse. 

In addition to the improved structure and cell connectivity, three-dimensional cultures have shown increased survival and enhanced neuronal differentiation compared to traditional mono-layer cultures [36, 37], The increased survival could be related to the improved cell-cell and cell-matrix contact as it leads to improved cell signaling and gap junction connections. Also cellcell signaling can promote proliferation of glial and NSCs that can contribute to increased culture survival. Moreover, the improved cellcell interaction in the 3D structure, especially between astrocytes and neurons, enhances neurogenesis, synapse formation, and axon myelination. 

There are regional asymmetries in membranes. Some, such as occur at the villous borders of mucosal cells, are almost macroscopicaUy visible. Others, such as those at gap junctions, tight junctions, and synapses, occupy much smaller regions of the membrane and generate correspondingly smaller local asymmetries. 

Synapses between the autonomic postganglionic neuron and effector tissue — the neuroeffector junction — differ greatly from the neuron-to-neuron synapses discussed previously in Chapter 5 (see Table 9.1). The postganglionic fibers in the ANS do not terminate in a single swelling like the synaptic knob, nor do they synapse directly with the cells of a tissue. Instead, the axon terminals branch and contain multiple swellings called varicosities that lie across the surface of the tissue. When the neuron is stimulated, these varicosities release neurotransmitter over a large surface area of the effector tissue. This diffuse release of the neurotransmitter affects many tissue cells simultaneously. Furthermore, cardiac muscle and most smooth muscle have gap junctions between cells. These specialized intercellular communications... 

FIGURE 1-11 An electro tonic synapse is seen at the surface of a motor neuron from the spinal cord of a toadfish. Between the neuronal soma (left) and the axonal termination (right), a gap junction flanked by desmosomes (arrows) is visible. (Photograph courtesy of Drs G. D. Pappas and J. S. Keeter.) X80,000. 

The biochemical properties of these structures are known. Desmosomes display protease sensitivity, divalent cation dependency and osmotic insensitivity and their membranes are mainly of the smooth type. In direct contrast to desmosomes, the tight junctions as well as gap junctions and synapses display no protease sensitivity, divalent cation dependency or osmotic sensitivity, while their membranes are complex. These facts have been used in the development of techniques to isolate purified preparations of junctional complexes. 

The communication between neurons occurs at either gap junctions (electrical synapses) or chemical synapses with release of neurotransmitters from a presynaptic neuron and their detection by a postsynaptic nerve cell (Fig. 17.1). Neurotransmitters not used in the synaptic cleft are removed promptly by either uptake into adjacent cells, reuptake in the presynaptic neuron, or are degraded by enzymatic systems. 

In certain neurons, a different type of synapse, called a gap junction, may be formed. Gap junction transmission occurs through membrane channels made of six subunits, which directly connect with other postsynaptic gap junction channels. When the channels open, there is a continuity of cytoplasm and exchange of ions between the two neurons. This mode of transmission is faster because it does not involve the time-consuming processes of neurotransmitter release, diffusion across the synapse, and receptor binding. 

Another type of communicating junction is also found in synapses of the nervous system. At these specialized contacts a nerve impulse transmitted along the membrane of one neuron triggers the release of a neurotransmitter, a chemical substance that passes across the gap between cells of the synapse and initiates a nerve impulse in the second neuron (Chapter 30). 

Figure 30-15 (A) Diagram of the two-dimensional tree formed by dendrites of a single Purkinje cell of the cerebellum. From Llinas.404 (B) Schematic diagram showing input and output pathways for Purkinje cells. (C) Recordings of output from four different neurons of the inferior olive. These action potentials are thought to arise from oscillations that arise within the neurons or within arrays of adjacent neurons coupled by electrical (gap junction) synapses. These oscillations synchronize the generation of action potentials so that some cells oscillate in synchrony while others (e.g., cell 4 above) do not. From McCormick.412...

Gap junctions in synapses. Not all neurons communicate via chemical synapses. Gap junctions, which are found in both neurons, astrocytes, and other cells, serve as electrical synapses. Thus, heart cells are all electrically coupled together by gap junctions.606-608 Gap junctions are formed with the aid of hexameric connexons, which are present in each of the opposed membranes and are aligned one with the other (Fig. 1-15F,G).607 609 610 There may be thousands of connexons in a single gap junction, which resemble ion channels in appearance but contain pores 1.5 nm in diameter. They are formed from 26- to 43- kDa... 

As can be seen from Fig. 30-32, neurons send "trains" of spikes down their axons. These form synapses with dendrites, usually on dendritic spikes, of a postsynaptic cell.593,1007-1009 However, each such cell typically receives input from thousands of other neurons. At any moment most of these are probably "silent," but others are sending trains of impulses. Among the important questions are "How does the postsynaptic neuron know whether to fire or not " and "What kinds of information, if any, are encoded in the trains of impulses both in the presynaptic inputs and in the output of the postsynaptic neuron "10101011 Part of the answer to the first question is probably that firing occurs if two or more input impulses arrive synchronously,10101012-1014 and if there are not too many inhibitory impulses that damp the response. In the hippocampus a network of neurons electrically coupled via gap junctions may be synchronized to the theta and gamma brain rhythms by high-frequency (150-200 Hz) oscillations.988 See also Fig. 30-15. 

Pathways in the central nervous system. A shows two relay neurons and two types of inhibitory pathways, recurrent and feed-forward. The inhibitory neurons are shown in black. B shows the pathway responsible for presynaptic inhibition in which the axon of an inhibitory neuron synapses on the axon terminal of an excitatory fiber. C Diagram illustrating that dendrites may be both pre-and postsynaptic to each other, forming reciprocal synapses, two of which are shown between the same dendrite pair. In triads, an axon synapses on two dendrites, and one of these dendrites synapses on the second. In serial synapses, a dendrite may be postsynaptic to one dendrite and presynaptic to another, thus connecting a series of dendrites. Dendrites also interact through low-resistance electrotonic ("gap") junctions (two of which are shown). Except for one axon, all... 

Bone cells are electrically active [10, 11, 24, 121, 170]. In addition to permitting the intercellular transmission of ions and small molecules, gap junctions exhibit both electrical and fluorescent dye transmission [93, 183, 187, 133], Gap junctions are electrical synapses, in contradistinction to intemeur-onal, chemical synapses and, significantly, they permit bi-directional signal traffic (e.g., biochemical, ionic, electrical etc.). In a physical sense, the CCN represents the hard wiring [30, 140, 141, 150] of bone tissue. 

As noted above, gap junctions as electrical synapses permit bi-directional flow of information. This is the cytological basis for the oscillatory behavior of a CCN. The presence of sharp discontinuities between groups of pheno-typically different osteoblasts is related also to an associated property of gap junctions, i.e., their ability to close and so prevent the flow of information [98, 106], Significantly, informational networks can also transmit inhibitory signals, a matter beyond our present scope [116],... 

Gap junctions provide in the nervous system the structural correlate of one class of electrical synapses, characterized by very close apposition between the presynaptic and postsynaptic membranes. It should be noted, in this respect, that different junctional specializations can mediate different forms of electrical transmission between neurons (Bennett, 1997). Electrical synapses transmit preferentially, but not exclusively, low-frequency stimuli, that allow the rapid transfer of a presynaptic impulse into an electrical excitatory potential in the postjunctional cells. Electrical transmission, via the intercellular channels, can be bidirectional. The widely held opinion that electrical transmission is characteristic of lower vertebrates probably derives from the large cell systems in which electrical synapses were identified in the initial period of intracellular recording (reviewed by Bennett, 1997). Contradicting this view, electrotonic coupling between neurons has now been demonstrated in many areas of the mammalian central nervous system and has been implicated in neuronal synchronization. Gap junctional intercellular communication can occur between glial cells, glia and neurons, as well as between neurons. 

Electrical synapses, which are tubular structures (called connexions) and form gap junctions the membranes of the two cells are separated by a distance of 2 nm. They may allow the two-way transmission of impulses ... 

Kosaka T, Kosaka K. 2005. Intraglomerular dendritic link connected by gap junctions and chemical synapses in the mouse main olfactory bulb Electron microscopic serial section analyses. Neuroscience 131 611-625. 

At the ultrastructural level the majority of the release sites (65-70%) appear as a single cluster of synaptic vesicles accumulated at a single active zone (Fig. ID), which may contain specializations of pure chemical or mixed synapses (Pfenninger and Rovainen, 1974 Ringham, 1975 Christensen, 1976 Rovainen, 1979). The latter type thus contains gap junctions as well as active zones (Fig. ID). Most of the synapses are established on dendritic shafts. A distinct class of intemeuron, however, receives axo-somatic synapses (OS and LB unpublished). The majority of the postsynaptic cells receive multiple chemical or mixed synaptic contacts from a single axon. Therefore most of the EPSPs recorded in postsynaptic neurons are composed of two components, an electrotonic and a chemical component. 

---