Table 2.

Glutamatergic dysfunctions reported in pharmacological and genetic animal models of ASD.

Mouse Model	Alterations in Glutamatergic Signaling	Refs.
FMR1 KO (Fragile X)	High expression of the AMPAR subunit GluR1-4 in the hippocampal CA1 pyramidal neurons and Purkinje Cells of the cerebellum.	[214,215]
	Lower levels of NMDAR expression.	[216]
	Early transient increase in AMPAR/NMDAR ratio and increased expression of the GluA2 subunit in synaptic AMPARs.	[217,218]
	The mGlu5 antagonist MPEP improved NMDA-mediated deficits in LTP.	[8]
	Altered forms of synaptic plasticity mediated by overactivation of mGlu5.	[219,220]
VPA model	Alterations in E/I balance.	[207]
	Alterations in Glu receptor expression and synaptic transmission.	[52]
	Increased NMDA receptor expression and long-term potentiation.	[221,222]
SHANK2 KO	Reduced levels of several cell surface Glu receptors in striatum and thalamus.	[223]
	mGlu1 antagonist ineffective in rescuing the social deficits in SHANK2 KO rats	[224]
SHANK3 KO	Reduced levels of several cell surface Glu receptors in striatum and thalamus. Alterations in AMPAR expression.	[223]
	NMDAR dysfunction	[225]
	Altered forms of synaptic plasticity mediated by mGlu	[226]
NLGN1-2-3 KO	Alterations in AMPAR expression in brainstem neuronal cultures. Alterations in the frequency of spontaneous and miniature excitatory postsynaptic currents. No effect on evoked postsynaptic currents.	[227]
NLGN1 KO	The NMDA co-agonist d-cycloserine reduced anxiety and repetitive behavior	[228]
NLGN3-R704C	Altered AMPAR-mediated currents.	[229]
NLGN3-R451C	Increased NMDA/AMPA ratio in pyramidal neurons of the CA1 region of the hippocampus.	[230]
	Non-significant increase in the frequency of mEPSCs in the hippocampus.
	Increased expression of the excitatory postsynaptic scaffolding proteins PSD95 and SAP-102, and the GluN2B subunit of the NMDA receptor
BTBR	Decreased plasticity and excitatory postsynaptic potentials.	[231]