Gap junction proteins and the wiring (Rewiring) of neuronal circuits

Abstract

The unique morphology and pattern of synaptic connections made by a neuron during development arise in part by an extended period of growth in which cell-cell interactions help to sculpt the arbor into its final shape, size, and participation in different synaptic networks. Recent experiments highlight a guiding role played by gap junction proteins in controlling this process. Ectopic and overexpression studies in invertebrates have revealed that the selective expression of distinct gap junction genes in neurons and glial cells is sufficient to establish selective new connections in the central nervous systems of the leech (Firme et al. [2012]: J Neurosci 32:14265-14270), the nematode (Rabinowitch et al. [2014]: Nat Commun 5:4442), and the fruit fly (Pézier et al., 2016: PLoS One 11:e0152211). We present here an overview of this work and suggest that gap junction proteins, in addition to their synaptic/communicative functions, have an instructive role as recognition and adhesion factors. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 575-586, 2017.

Newly Identified Electrically Coupled Neurons Support Development of theDrosophilaGiant Fiber Model Circuit

“…The molecular pathways responsible for these phenotypes may be shared with the axon retraction caused by the loss of synaptic partners, with Highwire/MYCBP2, Wallenda/DLK, and Basket/JNK as prime candidates (Ghosh et al, 2011; Borgen et al, 2017). While gap junctions play extensive roles in neuronal development (Elias and Kriegstein, 2008; Belousov and Fontes, 2013; Baker and Macagno, 2017), it is unlikely that GFI loss results from the loss of electrical coupling only, as the total removal of gap junctions from the GFI does not cause axon retraction or neuronal cell death (Blagburn et al, 1999).…”

Purinergic modulation of neuronal gap junction circuits in the CNS of the leech

“…Perhaps befittingly, the genome of the medicinal leech encodes a total of 21 different innexin genes, 15 of which are expressed by the neurons and glial cells of the leech ganglion (Kandarian et al, ). Two of these, innexin 1 and 14, appear to be expressed pan‐neuronally, while the other 13 are found in distinct, smaller subsets of cells (Dykes et al, ; Dykes & Macagno, ; Kandarian et al, ) which in some cases define discrete electrically and dye‐coupled networks of cells (Baker & Macagno, ; Dykes & Macagno, ; Firme, Natan, Yazdani, Macagno, & Baker, ; Kandarian et al, ). Furthermore, individual leech neurons appear to express multiple innexin genes, and in different ratios, allowing the possibility of considerable heterogeneity in innexon composition and distribution within a cell (Kandarian et al, ; Yazdani, Firme, Macagno, & Baker, ).…”

Plasticity of the electrical connectome ofC. elegans

“…First, it is generally thought that the formation of electrical synapses is encoded by the neuron-type-specific expression of matching homo-or heteromeric hemichannels, which recognize each other in trans to assemble into a functional electrical synapse. Second, the specific composition of an electrical synapse is thought to endow an electrical synapse with specific conductive properties (Baker and Macagno, 2017;Goodenough and Paul, 2009;Mese et al, 2007;Miller and Pereda, 2017;Sohl et al, 2005). For example, the widespread electrical connectivity of neurons in the C. elegans nervous system clearly indicates that information flow through many of the electrical synapses must be directional and such directionality is likely encoded by the specific molecular composition of individual synapses.…”

“…Since entry into the dauer stage of C. elegans entails a substantial remodeling of behavior (Cassada and Russell, 1975;Gaglia and Kenyon, 2009;Hallem et al, 2011a;Lee et al, 2012) (more below), we reasoned that the connectome of the dauer might also be substantially distinct. Since the presence or absence of innexins in a cell are expected to have a profound impact on synaptic partner choice and synaptic properties (Baker and Macagno, 2017;Goodenough and Paul, 2009;Mese et al, 2007;Miller and Pereda, 2017;Sohl et al, 2005), we investigated the expression patterns of innexins in the dauer stage as proxy for the electrical synaptic connectivity. We found that 11 of the 14 innexin genes normally expressed in the nervous system in larval and adult stages change their expression in a strikingly neuron-specific manner (Fig.…”

“…the choice of which neurons engage in electrical synaptic contact, based on a matching assembly of innexin proteins in connected neurons; and (b) functional diversity, i.e. electrical synapses with distinct molecular compositions are thought to have different functional properties (Baker and Macagno, 2017;Goodenough and Paul, 2009;Mese et al, 2007;Miller and Pereda, 2017;Sohl et al, 2005).…”