Compartmentalization of neuronal function is achieved via specifically localized clustering of ion channels in discrete subcellular membrane domains. Transient receptor potential (TRP) channels exhibit highly variable cellular and subcellular patterns of expression. We previously revealed that the thermo-sensor TRPV4 (activated above 34 degrees C) is gated by physiological brain temperatures in hippocampal neurons and thereby controls their excitability. Here, we examined synaptic clustering of TRPV4 in developing hippocampal neurons. We found that TRPV4 accumulated in the soma of immature hippocampal neurons, and did not localize to post-synaptic locations although PSD-95-labeled post-synaptic structures were evident. During the maturation of neurons, TRPV4 was targeted to dendrites and also clustered at post-synaptic locations. Taken together, we reveal that TRPV4 localizes to post-synaptic sites and the post-synaptic targeting is strictly regulated in a neuronal maturation-dependent manner. (C) 2015 Elsevier Inc. All rights reserved.