Wadsworth for their help in programming and data collection for this study, respectively. This project was supported by the Department of Psychology faculty start-up funds and the McNulty-Civitan scientist award to RK.
The cell adhesion molecule L1 is a member of the immunoglobulin superfamily, and it is predominantly expressed by postmitotic neurons of the central nervous system (Rathjen and Schachner 1984; Maness and Schachner 2007). By activating diverse mechanisms such as homophilic and heterophilic adhesion, as well as signal transduction, Inhibitors,research,lifescience,medical L1 plays key roles in cell adhesion, neuronal migration and survival, neurite outgrowth, axonal fasciculation,

synaptic plasticity, and cognitive function (Sandi 2004; Maness and Schachner 2007). In humans, CX-5461 cell line mutations in the L1 gene cause obvious malformations Inhibitors,research,lifescience,medical to the brain, including ventricular dilatation and the abnormal formation of major axonal tracts (e.g., corticospinal tract, corpus callosum) (Brümmendorf et al. 1998; Kamiguchi et al. 1998). In vitro, L1 mutations

influence neurite outgrowth (Moulding et al. 2000; Cheng and Lemmon 2004) and L1-deficient mice have brain anomalies similar to those described in humans with L1 mutations. L1-null mice also have impaired distribution of tyrosine hydroxylase positive Inhibitors,research,lifescience,medical neurons in areas of the mesencephalon and diencephalon, mapping of retinal ganglion cell axons to the superior colliculus, and fasciculation of thalamocortical and corticothalamic fibers (Cohen et al. 1997; Dahmé et al. 1997; Fransen et al. 1998; Demyanenko et al. 1999, 2001; Rolf et al. 2001; Demyanenko and Maness 2003; Ohyama et al. 2004). L1 mutations Inhibitors,research,lifescience,medical are associated with some types of mental retardation in humans and it is has been demonstrated that L1 influences hippocampal function and behavior in rodents (Wong et al. 1995; Arami et al. 1996; Inhibitors,research,lifescience,medical Law et al. 2003; Sandi 2004; Maness and Schachner 2007). A clear relationship between

L1 expression and the alteration of neurotransmitter systems critical to cognitive functions has yet to be established. Gamma-aminobutyric acid (GABA)-ergic neurotransmission is reduced in the hippocampus of L1-deficient mice and this may have functional consequences in vivo (Saghatelyan et al. 2004). Septal cholinergic innervation to the hippocampus is known to be essential to cognitive functions (Sarter and Parikh 2005). Here, we investigated whether the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) and the development of septal cholinergic neurons are regulated by L1. We focus on and septal cholinergic neurons for several reasons, including the report on septal malformations in L1-deficient mice (Demyanenko et al. 1999) and the delayed growth of the medial septum in acallosal mice (Wahlsten and Bulman–Fleming 1994). Furthermore, we previously found that L1 is strongly expressed by developing septal neurons in vitro (Frappé et al. 2004) and by regenerating cholinergic septohippocampal axons in vivo (Aubert et al. 1998).