Unmet Need:
The ability of neurons to alter the strength of their synaptic inputs bidirectionally in response to different stimuli is known as synaptic plasticity. Synaptic plasticity allows the brain to encode and respond to different stimuli such as learning and memory. Synaptic strengthening and weakening are finely tuned by changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) -type glutamate receptors (AMPARs). However, the exact tyrosine residue(s) and whether these changes are necessary for AMPAR trafficking during homeostatic scaling remain elusive. There remains a strong need for mouse models that can further elucidate these molecular mechanisms.
Technology Overview:
Johns Hopkins researchers generated a mouse model with a Y876F point mutation in the glutamate receptor, ionotropic, AMPA2 (alpha 2) (GluA2) gene, a phosphorylation site which plays an important role in synaptic plasticity. AMPA receptors mediate fast excitatory synaptic transmission. These mouse models provided evidence that biochemical regulation of AMPARs is specific to homeostatic synaptic plasticity mechanisms.
Stage of Development:
Pre-clinical models are available from the Jackson Laboratory (Stock No. 037072).
Publication:
Yong AJH, et al., PNAS., 117(9):4948-4958, 2020
