Rationale: Expression of HCN channels in hippocampus is developmentally regulated, suggesting that these channels contribute to age-specific network functions (Bender, Neuroscience, 2001). We recently found that sub-cellular transport of the HCN1 channel isoform can also be age-dependent: In immature rats, HCN1 channels are abundantly expressed in the perforant path, in axons of entorhinal cortex (EC) layer II neurons. This expression weakens and virtually disappears with age (Bender, SFN, 2004). Because neuronal activity influences expression of HCN channels in developing hippocampus (Brewster, J Neurosci, 2002), we examined whether neuronal activity governs also the sub-cellular transport of these channels, using organotypic slice cultures, in which normal neuronal activity was maintained or blocked. Methods: Entorhino-hippocampal slice cultures were explanted on P4 and cultured for 7 days, with or without TTX (0.1 *micro*M) in the culture medium. HCN1 protein and mRNA expression were analyzed using immu...