Long-term depression (LTD) in the rodent superior colliculus (SC) is regarded as a model of synaptic refinement because it can be induced during development but not in adults. We investigated the role of transient receptor potential vanilloid type-1 (TRPV1) channels in this type of synaptic plasticity. Experiments were carried out in pigmented mice aged between postnatal day 8 (P8) and 42 (P42) and in adult mice. Retinal axons to the SC were labelled by injection of cholera toxin-beta (CTbeta) into the eye. Immunohistochemical staining for CTbeta, TRPV1 and markers of glutamatergic and GABAergic cells and fibres (VGLUT1 and VGAT or GAD65, respectively) was performed by using multiple immunofluorescence. This showed that both glutamatergic retinal afferents to, and some GABAergic neurones in, the superficial SC are TRPV1 positive in juvenile but not adult mice. Field potential recordings were made from the superficial grey layer in parasagittal SC slices, and LTD (76 +/- 8% of control responses) was induced with a 50 Hz, 20 s tetanus. Activation of TRPV1 with resiniferatoxin also reduced field potential amplitude to 84 +/- 8% of control values. Blockade of TRPV1 with the selective antagonist 5'-iodo-resiniferatoxin prevented the induction of LTD (98 +/- 4% of control values), but did not cause its reversal if LTD was already established. N-acylphosphatidylethanolamine-specific phospholipase D and 12-lipoxygenase, two proposed endovanilloid biosynthesizing enzymes, were co-expressed with TRPV1 in the SC at P14 and P28. These results suggest that TRPV1 modulates retinocollicular responses in the developing SC and is activated during tetanic stimulation by endovanilloid ligands to participate in the induction of LTD.