Regional distribution of the leucine-rich glioma inactivated (LGI) gene family transcripts in the adult mouse brain.

The leucine-rich glioma inactivated (LGI) gene subfamily contains four highly conserved members (LGI1, 2, 3 and 4), which have been described in human, mouse and other mammalians. Although their main roles remain unknown, LGI1 gene mutations have been found in human partial temporal lobe epilepsy. Moreover, previous studies showed that the products of these genes exert their function in the nervous system. The anatomical distribution of these gene transcripts in the brain might give some insight to elucidate their possible function. In this study, the pattern of expression of the four LGI genes was assessed in the brain of C57BL/6J adult mice by in situ hybridization. We found that the LGI1 transcript is mainly expressed in the dentate gyrus and CA3 field of the hippocampus. LGI2 and LGI4 genes, which showed a similar pattern of distribution with minor differences, were mostly expressed in the medial septal area, thalamic reticular nucleus and substantia nigra pars compacta. LGI3-expressing cells were distributed widespread, but were more consistently observed in the hippocampal formation, thalamic and hypothalamic nuclei, substantia nigra and reticular formation. In summary, LGI1 gene expression is very restricted to intrahippocampal circuitry, which might be related to its involvement in temporal lobe epilepsy. The patterns of expression of LGI2 and LGI4 genes are very similar and their distribution in the vertical limb of the diagonal band and in putative hippocampal interneurons suggests that the function of these genes might be related to the generation of hippocampal theta rhythm. Finally, LGI3 gene widespread expression in the brain suggests that its transcripts might be involved in a common cellular process present in different neuronal types.

Anatomical evidence for a ponto-septal pathway via the nucleus incertus in the rat.

Hippocampal theta activity is involved in sensory-motor integration and constitutes a functional basis for mnemonic functions. The medial septum-diagonal band of Broca (MS/DBv) is a key structure as pacemaker of the oscillation. In addition, some brainstem reticular structures are crucial for the activation of MS/DBv. Specifically, the nucleus reticularis pontis oralis (RPO) is considered the most effective pontine site for eliciting theta rhythm. Nevertheless, its connection with the MS/DBv is not direct. A previous study by our group pointed out that the nucleus incertus (NI) could be considered as a relay in this multisynaptic pathway. From this study, the stimulation of RPO increased the discharge rate of NI neurons in anesthetized rats and the lesion of the NI suppressed the RPO-elicited hippocampal theta. Those findings suggested a projection from RPO to NI, although the existing literature did not support this hypothesis. In order to clarify the dichotomy between the anatomical and the electrophysiological data, we performed a set of tracing studies. Anterograde tracer injections into RPO showed a profuse projection to NI. This connection was confirmed by retrograde tracer injections into NI. Injections of retrograde tracer in MS/DBv confirmed the intense NI-MS/DBv projection. Furthermore, simultaneous injections of anterograde and retrograde tracers into RPO and MS/DBv respectively resulted in a high-correlated pattern of terminal-like fibers over labeled somata in the NI. This study provides the first anatomical evidence of a ponto-septal pathway via the NI that contributes to generation and modulation the hippocampal theta activity.