Expression and function of the neuronal gap junction protein connexin 36 in developing mammalian retina

Abstract

With the advent of transgenic mice, much has been learned about the expression and function of gap junctions. Previously, we reported that retinal ganglion cells in mice lacking the neuronal gap junction protein connexin 36 (Cx36) have nearly normal firing patterns at postnatal day 4 (P4) but many more asynchronous action potentials than wild-type mice at P10 (Torborg et al. [2005] Nat. Neurosci. 8:72-78). With the goal of understanding the origin of this increased activity in Cx36-/- mice, we used a transgenic mouse (Deans et al. [2001] Neuron 31:477-485) to characterize the developmental expression of a Cx36 reporter in the retina. We found that Cx36 was first detected weakly at P2 and gradually increased in expression until it reached an adult pattern at P14. Although the onset of expression varied by cell type, we identified Cx36 in the glycinergic AII amacrine cell, glutamatergic cone bipolar cell, and retinal ganglion cells (RGCs). In addition, we used calcium imaging and multielectrode array recording to characterize further the firing patterns in Cx36-/- mice. Both correlated and asynchronous action potentials in P10 Cx36-/- RGCs were significantly inhibited by bath application of an ionotropic glutamate receptor antagonist, indicating that the increase in activity was synaptically mediated. Hence, both the expression patterns and the physiology suggest an increasing role for Cx36-containing gap junctions in suppressing RGC firing between waves during postnatal retinal development.

Development of Presynaptic Inhibition Onto Retinal Bipolar Cell Axon Terminals Is Subclass-Specific

“…AII amacrine cells are described to express functional TTX-sensitive sodium channels (Boos et al 1993;Tamalu and Watanabe 2007;Veruki and Hartveit 2002). Taken together with previous findings showing that electrical synapses between AII amacrine cells and ON-CBCs become functional by P10 (Hansen et al 2005;Pow and Hendrickson 2000), our current data suggest that the circuitry linking the rod bipolar and cone bipolar pathways is functional prior to the emergence of robust light responses.…”

“…Indeed, amacrine cells that we recorded between P7 and P9 showed an adult-like morphology, and some cells could be classified as A17 or AII amacrine cells. Additionally, AII amacrine cells have been identified previously by P8 by immunolabeling for disabled-1 (Hansen et al 2005).…”

Retinal anatomy and visual performance in a diurnal cone‐rich laboratory rodent, the Nile grass rat (Arvicanthis niloticus)

“…A complete loss of labeling was observed in sections of embryonic mouse spinal cord with this antiserum after preabsorption with 40 M of immunizing conjugate (Allain et al, 2005). The labeling pattern was consistent with that observed in previous studies of the mouse retina using this (Hansen et al, 2005;Moon et al, 2005) or different antibodies (Haverkamp and Wä ssle, 2000). The affinity-purified anticholine acetyltransferase (ChAT) antibody (raised against the human placental enzyme) detects an Ϸ70-kDa product in rat brain extract (manufacturer's data sheet).…”

NMDA Receptor Blockade Maintains Correlated Motor Neuron Firing and Delays Synapse Competition at Developing Neuromuscular Junctions

“…This suggests that synaptic inputs to motor neurons result in broad correlation during early postnatal development and that short-term correlations are only seen as spinal synaptic connections mature. Together, these results suggest that motor unit correlation during postnatal development is modulated by both gap junctional coupling between neurons and by local synaptic inputs to motor neurons, resulting in both short (Յ50 ms) and broad (100 ms to 2 s) correlated activity (Hu and Bloomfield, 2003;Hansen et al, 2005).…”

“…Because the strength of temporal correlations between motor units is increased in MK801-injected animals beyond that reported previously at any postnatal age, it suggests that other cellular mechanisms in conjunction with gap junctional coupling may modulate motor unit correlation during postnatal development. Thus, enhanced intrinsic motor neuron excitability, increased excitatory chemical synaptic connections, together with maintained gap junctional coupling among motor neurons and/or interneurons may result in the supernormal correlative motor activity seen after MK801 treatment (Hanson and Landmesser, 2004;Hansen et al, 2005).…”