BIPN 148 Lecture 12

Biochemical Basis of LTP

Interaction Between AMPAR, Stargazin, and PSD-95

Stargazin interacts with AMPA receptors in an intracellular compartment in the cell and promotes their delivery to the cell surface. The carboxyl terminus of stargazin binds specifically to the anchor protein PSD-95 and mediates recruitment of the stargazin-AMPA receptor complex to postsynaptic sites.

Loss of AMPA current in stargazer mutant mice

(recordings from cerebellar granule neurons)

Stargazin enhances glutamate response

Stargazin restores AMPA currents in mutants

(Stargazin-deltaC restores surface expression, but not synaptic targeting)

PSD95 and Stargazin have distinct effects on synaptic responses and surface AMPA receptors

Stargazin-deltaC inhibits AMPA responses

Stargazin increases AMPA channel openings

Stargazin increases surface GluR1 expression

GluR1-C tail expression inhibits LTP

Effect of GluR1 S887A (C tail) on LTP

Role of GluR1 trafficking in fear conditioning: Physiology of GluR1 transfected neurons in Amygdala

Expression of GluR1-C inhibits plasticityin Amygdala

Expression of GluuR1-C inhibits fear conditioning