Gap junctions mediate electrical coupling between

Gap junctions mediate electrical coupling between cells by conducting direct ionic currents and thereby modulate their electrical activity (Hormuzdi et al., 2004). In the nervous system, electrical coupling organizes network activity by amplifying and synchronizing neuronal firing (Galarreta and Hestrin, 1999, Bennett and Zukin, 2004). Although neocortical pyramidal neurons rarely exhibit electrical coupling in the mature find molarity (Gibson et al., 1999), gap junctions are observed in pyramidal neurons during development. Sister pyramidal neurons in the mouse neocortex exhibit electrical coupling around the first half of the first postnatal week (Yu et al., 2012), and layer 4 pyramidal neurons in the barrel cortex are coupled during the first postnatal week (Valiullina et al., 2016). These gap junctions disappear during postnatal development and are implicated in the development of neuronal circuits. Recent evidence indicates that pyramidal neurons in mouse layer 5 form a dense, cell type-specific gap junction network during development. Neocortical layer 5 contains two major types of pyramidal neurons, subcerebral projection neurons (SCPNs) that innervate subcortical targets, including the pons and superior colliculus, and callosal projection neurons (CPNs) that innervate the contralateral cortex (Molyneaux et al., 2007). These two types of pyramidal neurons organize into cell type-specific and lineage-independent radial clusters termed microcolumns that exhibit modular neuronal activity (Maruoka et al., 2011, Maruoka et al., 2017). Whereas coupling probability of sister neuron pairs declines during the first postnatal week to ~2% at postnatal day 6 (P6) (Yu et al., 2012), at the beginning of the second postnatal week, when chemical synapse formation is initiated (Li et al., 2010, Ashby and Isaac, 2011), SCPNs and CPNs are frequently coupled with neurons of the same type (Maruoka et al., 2017, Chevée and Brown, 2018). This coupling occurs between ~50% of neighboring and radially aligned neuron pairs and therefore densely couples neurons in the same microcolumns. Lineage tracing experiments suggested that this coupling is independent of lineage (Maruoka et al., 2017). Electrical coupling of SCPNs and CPNs disappears during the second postnatal week and becomes undetectable at the stage of eye opening. These observations suggest the possibility that the cell type-specific and lineage independent gap junction network organizes neuronal activity of developing modular cortical circuits. However, modulation of neuronal activities has not been shown, and the properties of such modulation are unknown.
The present study demonstrated that electrical coupling of layer 5 pyramidal neurons amplifies firing activity and facilitates slow synchronization. Given that the electrical coupling is present at the stage of synaptogenesis, gap junction-mediated synchronized and amplified activity may facilitate the development of synaptic circuits. Because electrical coupling occurs for SCPNs and CPNs in a cell type-specific manner, modulation of neuronal activity may underlie the development of neuronal circuits specific to SCPNs and CPNs (Morishima and Kawaguchi, 2006, Brown and Hestrin, 2009, Anderson et al., 2010, Morishima et al., 2011). Gap junctions densely couple neurons in single microcolumns and likely synchronize their activity, and may facilitate the development of synaptic circuits specific to individual microcolumns, such as synaptic inputs common to neurons in the same microcolumns (Maruoka et al., 2017). In the present study, we examined AP amplification and synchronization by injecting electrical currents into two neurons. Because approximately 50% of neighboring and radially aligned pairs of the same type of neuron are coupled (Maruoka et al., 2017), single pyramidal neurons likely couple with multiple neurons. Therefore, a considerable amount of injected currents may have flowed out to neurons that were not recorded in our experimental conditions. In vivo cortical activity, such as retina-driven waves, may provide coincident input into a larger group of coupled neurons and induce stronger amplification and synchronization.