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Table 1 Repetitive behaviors and neuronal phenotypes in ASD mouse models

From: Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder

Type of repetitive behaviors Model mouse Biological functions of the target protein Other behavioral characteristics Implicated brain regions and neural phenotypes Rescue of repetitive behaviors
Self-grooming BTBR T + tf/J (inbred strain) [16]   Hyperactive
Impaired cognitive flexibility [83, 84]
Decreased sIPSC and increased sEPSC frequency in the hippocampus [27]
No corpus callosum [24]
Repetitive self-grooming and E/I balance with GABA-R agonists such as clonazepam [34]
Repetitive self-grooming with mGluR5 antagonism [32, 33]
Repetitive self-grooming with a NMDA-R agonist, d-cycloserine [85]
Scn1a +/− [13] A voltage-gated sodium channel NaV1.1 as a primary sodium channel specifically in GABAergic neurons Hyperactive [13] Decreased sIPSC and increased sEPSC frequency in the hippocampus and prefrontal cortex [13]  
Cntnap2 −/− [28] A kind of neurexin family, implicated in neuron-glia interactions and K+ cahnnel clustering [28] Hyperactive [28] Decreased GABAergic neurons in the corpus callosum, somatosensory cortex, and striatum [28] Repetitive self-grooming with a D2R antagonist, risperidone [28]
NRXN1α −/− [86] A presynaptic protein that binds to postsynaptic protein, neuroligin, forming and strengthening synapses Hypoactive [87] Decreased mEPSC frequency in the hippocampus [86]  
Expression of dominant negative mutation of neurexin 1β [88]   Decreased mEPSC and mIPSC frequency in the somatosensory cortex [88]  
Shank3b −/− [34] A scaffolding and postsynaptic density (PSD) protein found at glutamatergic synapses, forming complexes with PSD95, SAPAP, Homer, and GKAP
Implicated in 22q13 deletion syndrome (Phelan–McDermid syndrome),
Self-injurious grooming
Decreased rearing [34]
Decreased cortico-striatal pop-spike amplitude [34]  
En2 −/− [89] A transcription factor which is important for development, including neuronal differentiation of the mid/hind brain [90] Hyperactive (only p21–27) [89] Decreased GABAergic neurons in the hippocampus and cerebral cortex [90]  
Ephrin-A −/−
Ephrin-A3 −/− [91]
A ligand of cell-surface ephrin receptor implicated in development and synaptic plasticity of neurons [92, 93] Self-injurious grooming
Hypoactive
Decreased rearing [91]
`  
Shank1 −/− [94] A scaffolding and PSD protein found at glutamatergic synapses, forming complexes with PSD95, SAPAP, Homer, and GKAP Hypoactive Impaired rotarod performance [94] Smaller dendrites and thinner PSDs in hippocampal neurons
Decreased mEPSC in the hippocampus
Decreased input–output (I/O) curve in the hippocampus [94]
 
Eif4ebp2 −/− [95] Initiation of translation by leading eukaryotic mRNA to ribosomes   Increased mEPSC amplitude and frequency
Increased mIPSC amplitude
Increased net E/I ratio in the hippocampus [95]
 
Viaat (vesicular inhibitory amino acid transporter)-Mecp2 −/y [96] Suppression or activation of target genes and implicated in Rett syndrome Hypoactive [96] Decreased mIPSC amplitude in cortical slices
Impaired LTP in the hippocampus
Mecp2 depletion in inhibitory neurons [96]
 
Jumping C58/J [32]   Hyperactive Hypersensitivity to amphetamine [17, 32]   Repetitive jumping with a mGluR5 negative allosteric modulator, GRN-529 [25]
Shank2 −/− [12] A scaffolding and PSD protein found at glutamatergic synapses, forming complexes with PSD95, SAPAP, Homer, and GKAP Hyperactive
Decreased digging [12]
Decreased NMDA/AMPA ratio
Impaired LTP and LTD in the hippocampus [12]
 
NL2 overexpression [79] An adhesion molecule binding with presynaptic neurexins, regulating excitatory and inhibitory synaptic functions   Enlarged synaptic contact size
Increased mIPSC frequency in PFC
Decreased E/I balance in PFC [79]
 
Circling Scn1a +/− [13]   Hyperactive [13] Decreased sIPSC and increased sEPSC frequency in the hippocampus and prefrontal cortex [13]  
Gabrb3 −/− [97] A subunit of GABA-R, a chloride channel, implicated in ASD and seizure Decreased rearing [97] Hypoplasia of the cerebellar [97]  
Decreased marble burying Shank1 −/− [39]   Decreased rearing [39]   
Ephrin-A −/−
Ephrin-A3 −/− [91]
A ligand of cell-surface ephrin receptor implicated in development and synaptic plasticity of neurons [92, 93] Self-injurious grooming
Hypoactive
Decreased rearing [91]
`  
C58/J) [32]   Hyperactive
Hypersensitivity to amphetamine [17, 32]
  
Glutamate receptor, ionotropic, N-methyl D-aspartate 1 (Grin1) knock-down [11] An NMDA-R subunit implicated in synaptic plasticity Hyperactive
Decreased anxiety [72]
  
Increased marble burying BTBR [16]   Hyperactive
Impaired cognitive flexibility [83, 84]
Decreased sIPSC and increased sEPSC frequency in the hippocampus [27]
No corpus callosum [24]
 
Eif4ebp2 −/− [95] Initiation of translation by leading eukaryotic mRNA to ribosomes   Increased mEPSC amplitude and frequency
Increased mIPSC amplitude
Increased net E/I ratio in the hippocampus [95]
 
FMR1 −/− [98] Regulation of hundreds of mRNAs in the synapses
Depletion of FMR1 leads to fragile X syndrome
Hyperactive [99] Hyper-excitability caused by decreased activities of fast-spiking (FS) inhibitory neurons in the somatosensory, barrel cortex. [100]  
Rearing C58/J [32]   Hyperactive Hypersensitivity to amphetamine [11, 24]   
Head poking Shank3 −/− [101]   Hypoactive [101] Increased spine length in the hippocampus
Decreased mIPSC frequency and Impaired LTP in the hippocampus [101]
 
Forelimb movements Expression of truncated Mecp2 [102] Suppression or activation of target genes and implicated in Rett syndrome Hypoactive Motor deficits [102]   
Viaat-Mecp2 −/y [96]   Decreased mIPSC amplitude in cortical slices
Impaired LTP in the hippocampus
Mecp2 depletion in inhibitory neurons [96]
 
Hanging Expression of SERT Ala56 [103] Returns serotonin excreted into the synaptic cleft to the presynaptic boutons   Decreased firing in dorsal raphe neurons
Hyperserotonemia [103]