Table 1.

Summary table of synaptic transmission examined in neurexin mutant mouse models.

Neurexin targeted in mouse models	Brain region examined	Genetic approach/manipulation	Main findings in synaptic function	References
Nrxn1α, β, or αβ	Cortex1, Hippocampus2,3	Conditional KO1	Nrxn1β KO decreased mEPSCs and mIPSCs frequency in cortical layer 5/6 pyramidal neurons1	Rabaneda et al.(2014)1
		Constitutive KO2	Nrxn1α KO reduced spontaneous release in excitatory glutamatergic synapses without any effect on inhibitory transmission in pyramidal neurons in the CA1 region of the hippocampus2	Etherton et al. (2009)2
		Conditional KI3	Conditional KI of SS4+ in Nrxn1 increased NMDARs-mediated EPSCs without affecting AMPARs-mediated EPSCs in the CA1-subiculum synapses in the hippocampus3	Dai et al. (2019)3
Nrxn2α, β, or αβ	Hippocampus3,5,6	Conditional KI3	Conditional KI of SS4+ in Nrxn2 lead to no change in NMDAR and AMPAR-mediated EPSCs3	Dai et al. (2019)3
	Cortex4	Constitutive KO4,5	Constitutive KO of Nrxn2α and Nrxn2αβ reduced spontaneous transmitter release at excitatory synapses in the neocortex. Both KO mice exhibited altered facilitation and NMDAR function due to a reduction in NMDAR-dependent decay time and responses in excitatory synapses. Inhibitory transmission and synapse densities and ultrastructure remained unchanged in both Nrxn2α and Nrxn2αβ KO4	Born et al. (2015)4
		Conditional KO5,6	Constitutive deletion of Nrxn2 gene increases hippocampal CA3 to CA1 synaptic connections. Conditional (Neuron-specific) deletion of Nrxn2 gene also increases CA3 to CA1 synaptic connectivity, and release probability, and increases excitatory synapse density in the CA1 region5	Lin et al. (2023)5
			Conditional (Emx1Cre driven) deletion of Nrxn2 gene increased network activity in hippocampal circuities as measured by increased sEPSC and sIPSC frequencies independent of changes in neurotransmitter release probability or changes in AMPARs and NMDARs contributions6	Haile et al. (2022)6
Nrxn3α, β, or αβ	Hippocampus3,7	Conditional KI3	Conditional KI of SS4+ in Nrxn3 suppressed AMPARs-mediated synaptic responses without any effect on NMDARs function in the same synapses3	Dai et al. (2019)3
		Constitutive KI7	Constitutive KI of SS4+ in Nrxn3 caused a decrease in AMPARs mediated synaptic responses in hippocampal synapses7	Aoto et al. (2013)7
	Olfactory bulb8	Conditional KO8	Conditional deletion of Nrxn3 gene in the CA1 region of the hippocampus decreased (AMPARs)-mediated excitatory response and blockade of NMDARs-mediated LTP. In olfactory bulb synapses however, conditional deletion of Nrxn3 gene decreased GABAergic mediated inhibitory responses8	Aoto et al. (2015)8
Nrxn123α, β, or αβ	Cortex9,11, Hippocampus12,14 Brain Stem9,10,13,14 Cerebellum 11,14 Striatum15	Constitutive KO9,10	Constitutive deletion of Nrxn1/2/3 (only α-neurexins) reduced presynaptic Ca2+ influx, number of GABAergic terminals, and reduced spontaneous and evoked neurotransmitter release in neocortical neurons9	Missler et al. (2003)9
			Constitutive KO Nrxn1/2/3 (only α-neurexins) showed that they regulate N and P/Q type Ca2+ channels10	Zhang et al. (2005)10
		Conditional KO11,12,13,14,15	Conditional ablation of neurexins from parvalbumin-positive interneurons in the prefrontal cortex caused a loss of synapses without any effect on action-potential induced Ca2+ influx, or synaptic strength. Conditional ablation of neurexins from somatostatin-positive interneurons in the same brain region impaired action-potential induced Ca2+ influx and decreased synaptic strength without changes in number of synapses11	Chen et al. (2017)11
			Conditional KO of Nrxn1/2/3 (only β-neurexins) showed that they regulate postsynaptic endocannabinoid signaling through suppressing CB1 receptor agonist 2AG synthesis in hippocampal synapses. Despite the low expression of β-neurexins, cKO of Nrxn1/2/3 (only β-neurexins) lead to a two-fold decrease in EPSC amplitude, release probability, and action potential induced Ca2+ influx12	Anderson et al. (2015)12
			Conditional KO of Nrxn1/2/3 (all α-and β-neurexins) at the Calyx of Held synapses revealed neurexins regulate neurotransmission through coupling of presynaptic calcium channels to release sites13	Luo et al. (2020)13
			Conditional KO of Nrxn1/2/3 (all α-and β-neurexins) from four central synapses: excitatory Calyx of Held synapses in the brainstem, excitatory and inhibitory synapses in pyramidal neurons in the CA1 region of the hippocampus, and inhibitory basket cell synapses in the cerebellum, showed that neurexins universally regulate presynaptic GABAB-receptor signaling, albeit at different magnitude between synapses14	Luo et al. (2021)14
			Conditional KO of Nrxn 1/2/3 (all α-and β-neurexins) in DA neurons, showed (1) region-specific increase in GABA release from DA terminals (increase in the ventral but not in the dorsal striatum) and (2) slower DA reuptake along with decreased and increased densities of DAT and VMAT2, respectively15	Ducrot et al. (2021)15

KO, knockout; KI, knockin; mEPSCs, miniature excitatory postsynaptic currents; mIPSCS, miniature inhibitory postsynaptic currents; NMDARs, N-Methyl-D-aspartate receptors; AMPARs, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; EPSCs, excitatory postsynaptic currents; sEPSCs, spontaneous excitatory postsynaptic currents; sIPSCs, spontaneous inhibitory postsynaptic currents; LTP, long-term potentiation; GABA, γ-aminobutyric acid; DA, dopamine; DAT, dopamine transporter; VMAT2, vesicular monoamine transporter-2. Superscript numbers listed under “brain region examined”; “Genetic approach/manipulation” and “Main findings in synaptic function” corresponds to the respective study listed under “References.”