Numerous synaptic intracellular proteins interact with the intracellular C-terminal domain of glutamate receptor (GluR) subunits and control the receptor channels' gating, signaling or trafficking to and from the postsynaptic membrane. Many protein interactions have been physiologically investigated on synaptic currents in neurons of acute slices loaded with interacting peptides and in neurons of slice cultures infected with Sindbis virus expressing peptides, wild-type or mutated proteins. While Sindbis virus is a useful tool for rapid heterologous protein expression, Lentivirus can be used for stable protein expression. Furthermore, Lentivirus is not toxic and can be stereotactically delivered to brain regions of choice at any postnatal stage (Dittgen et al., 2004). Here, we stereotactically delivered lentiviral particles expressing EGFP into the hippocampal CA1 region of P21 mice and confirmed in acute slices, two weeks after the infection, that infected and non-infected neurons were electrophysiologically indistinguishable. Protein protein interactions are currently investigated by Lentivirus based expression of GluRs in GluRko mice or by means of protein knockdown using short interfering RNAs (siRNAs), two weeks post-infection, recording synaptic currents in acute hippocampal slices and determining their AMPA/NMDA current ratios, rectification ratios, activation and inactivation kinetics.