GRIA

GRIA refers to the gene family that encodes four subunits of the AMPA-type ionotropic glutamate receptor: GRIA1 (GluA1), GRIA2 (GluA2), GRIA3 (GluA3), and GRIA4 (GluA4). These subunits assemble as tetrameric receptors and form the primary mediators of fast excitatory synaptic transmission in the central nervous system.

AMPA receptors are ligand-gated cation channels opened by glutamate. They conduct sodium and, depending on subunit composition, calcium ions, contributing to synaptic depolarization and signaling. The GluA2 subunit, when edited at the Q/R site, renders the receptor calcium-impermeable, which strongly influences neuronal excitability. Subunit composition, RNA editing, and alternative splicing into flip and flop isoforms shape receptor kinetics, permeability, and trafficking.

GRIA genes are broadly expressed in the brain, with regional and developmental differences in their regulation. Receptors are dynamically trafficked to and from the synapse in response to activity, a process central to synaptic plasticity and mechanisms such as long-term potentiation and long-term depression.

Genetic alterations in GRIA genes have been linked to neurodevelopmental disorders, including intellectual disability and epilepsy. Autoimmune encephalitis can also involve antibodies against AMPA receptor subunits, causing rapid neuropsychiatric symptoms. Pharmacologically, AMPA receptors are targets for drugs that modulate their activity, including antagonists used in epilepsy and positive allosteric modulators explored for cognitive enhancement.