The spatial and temporal pattern of fatty acid amide hydrolase expression in rat hippocampus during postnatal...

GABAergic synaptic transmission is efficiently controlled by endogenous cannabinoids in cortical structures. Fatty acid amide hydrolase (FAAH) is one of the metabolizing enzymes of endocannabinoids in the brain. In this study we investigated the cellular and subcellular distribution of FAAH at various timepoints during the first postnatal weeks, when GABA is still depolarizing, and plays a crucial role in network events. FAAH immunoreactivity is strong in the CA3 region already at postnatal day 0 (P0), but in CA1 only after P8. During this period, FAAH levels in hilar mossy cells decrease and in granule cells slowly increase. Pyramidal cells express FAAH first in the soma and proximal dendrites, and gradually in more distal segments, reaching adult levels in the most distal dendrites only at P22. Transient expression of FAAH was found in a small number of stratum radiatum cells that may be interneurons and in ependymal cells at the border of the alveus and corpus callosum between P2 and P8. At the ultrastructural level, FAAH distribution at all ages was very similar to the adult pattern, i.e. it was largely associated with the membrane of cytoplasmic vesicles, mitochondria and endoplasmic reticulum. During postnatal development of the hippocampus, the spatio-temporal expression of FAAH correlates well with the general pattern of neuronal maturation, but not with the arrival of afferent pathways, which suggests that FAAH - and its major endocannabinoid substrate, anandamide - is unlikely to be involved in the presynaptic control of neurotransmission. Instead, FAAH may subserve general roles as the inactivating enzyme for many fatty acid amides, in addition to anandamide.