Electrophysiological Approach to GPCR-RTK Interaction Study in Hippocampus of Adult Rats

The allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) heteroreceptor complexes provided a new dimension for the integration of signaling at plasma membrane level of neurons in brain. Neuronal plasticity processes underlying brain functions, such as learning and memory, have been proposed to be based on rearrangement of heteroreceptor complexes and protomer interactions in the postsynaptic membrane. Among the different partners for GPCRs to form heteromers, receptor tyrosine kinases (RTKs) represent an intriguing combination due to their possible involvement in brain diseases. Different methodologies are available to study heteroreceptor complexes in brain tissue, but their functional role in modulating neuron electrical activity can be properly evaluated using an electrophysiological approach. Here, we describe patch clamp technique protocol for studying GPCR-RTK interaction in hippocampus CA1 pyramidal neurons of adult rat, paying particular attention to highlight major problems that can occur using this technique and providing useful troubleshooting steps to achieve reliable results.