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The Na/K/Cl cotransporter-1 (NKCC1) and the K/Cl cotransporter-2 (KCC2) set the transmembrane Cl gradient in the brain, and are implicated in epileptogenesis. We studied the postnatal distribution of NKCC1 and KCC2 in wild-type (WT) mice, and in a mouse model of sleep-related epilepsy, carrying the mutant β2-V287L subunit of the nicotinic acetylcholine receptor (nAChR). In WT neocortex, immunohistochemistry showed a wide distribution of NKCC1 in neurons and astrocytes. At birth, KCC2 was localized in neuronal somata, whereas at subsequent stages it was mainly found in the somatodendritic compartment. The cotransporters' expression was quantified by densitometry in the transgenic strain. KCC2 expression increased during the first postnatal weeks, while the NKCC1 amount remained stable, after birth. In mice expressing β2-V287L, the KCC2 amount in layer V of prefrontal cortex (PFC) was lower than in the control littermates at postnatal day 8 (P8), with no concomitant change in NKCC1. Consistently, the GABAergic excitatory to inhibitory switch was delayed in PFC layer V of mice carrying β2-V287L. At P60, the amount of KCC2 was instead higher in mice bearing the transgene. Irrespective of genotype, NKCC1 and KCC2 were abundantly expressed in the neuropil of most thalamic nuclei since birth. However, KCC2 expression decreased by P60 in the reticular nucleus, and more so in mice expressing β2-V287L. Therefore, a complex regulatory interplay occurs between heteromeric nAChRs and KCC2 in postnatal forebrain. The pathogenetic effect of β2-V287L may depend on altered KCC2 amounts in PFC during synaptogenesis, as well as in mature thalamocortical circuits.

Odorants are volatile molecules that efficiently carry chemical information, providing one of the main ways for communicating with the environment in all kingdoms of life. In the other hand, mammalian genomes codify for hundreds of olfactory receptors (ORs), e.g. about 400 in human and more than 1000 in mouse, underlying the crucial role of the sense of smell during evolution. Therefore, the olfactory system is capable to discriminate between ~10,000 different odors. The possibility of collecting and compiling information about odorants and their receptors is thus fundamental for a functional characterization of the signaling firing event. OlfactionDB, a manually curated database providing comprehensive information for nearly 400 odorant-receptor interactions at the current state, has been developed for managing information about odorants and their receptors. OlfactionDB is a free publicly database available online from: http://molsim.sci.univr.it/OlfactionDB.

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