The electrophysiological consequences of the Nlgn3R451C mutation in particular have been studied extensively. These mice have increased mIPSC frequency and eIPSC amplitude in layer 2/3 somatosensory cortex neurons (Tabuchi et al., 2007). However, they have decreased eIPSC amplitude in spiny neurons that receive input from PV-expressing basket cells in layer IV barrel cortex (Cellot and Cherubini, 2014). The R451C mutation also leads to an increased frequency of giant depolarizing potentials (GDPs) and mIPSCs in the CA3 region of the hippocampus starting during the first two weeks of postnatal life (Pizzarelli and Cherubini, 2013). These mice also exhibit increased excitatory transmission, increased LTP, and a decreased AMPA/NMDA current ratio in the CA1 region of the hippocampus (Etherton et al., 2011a). While most studies failed to find similar deficits in Nlgn3 knockout mice, one study found that both the Nlgn3R451C mice and Nlgn3 knockout mice have increased GABAergic synaptic transmission (eIPSCs) in cholecystokinin (CCK) basket cells and impair tonic endocannabinoid (ECB) signaling (Földy et al., 2013). Mice lacking Nlgn3 also have decreased frequency of mIPSCs in D1-MSNs of the NAc while having normal frequency of mEPSCs, thereby increasing the excitatory/inhibitory current ratio (Rothwell et al., 2014).
