Acetylcholine Inhibits Spontaneous Firing Activity of Terminal Nerve GnRH Neurons in Medaka.

Vertebrates generally possess hypophysiotropic and non-hypophysiotropic gonadotropin releasing hormone (GnRH) neurons. The terminal nerve (TN) GnRH neurons are known to belong to the non-hypophysiotropic neurons and have been suggested to modulate sexual behaviors. These neurons show spontaneous pacemaker firing activity and release neuropeptides GnRH and neuropeptide FF. Since the spontaneous firing activities of peptidergic neurons, including GnRH neurons, are believed to play important roles in the release of neuropeptides, understanding the regulatory mechanisms of these spontaneous firing activities is important. Here, we analyzed firing activities of the TN-GnRH neurons in medaka during application of acetylcholine (ACh), which is one of the essential neuromodulators in the brain. Whole cell patch clamp recording of TN-GnRH neurons demonstrated that ACh induces hyperpolarization and inhibits their pacemaker firing. Electrophysiological analysis using an antagonist for acetylcholine receptors and in situ hybridization analysis showed that firing of TN-GnRH neurons is inhibited via M2-type muscarinic acetylcholine receptor. These findings, taken together with literature from several other fish species (including teleosts and elasmobranchs), indicate that ACh may generally play an inhibitory role in modulating spontaneous activities of TN-GnRH neurons and thereby sexual behaviors in fish.

The LPA-LPA4 axis is required for establishment of bipolar morphology and radial migration of newborn cortical neurons.

Newborn neurons in the developing neocortex undergo radial migration, a process that is coupled with their precise passage from multipolar to bipolar shape. The cell-extrinsic signals that govern this transition are, however, poorly understood. Here, we find that lysophosphatidic acid (LPA) signaling contributes to the establishment of a bipolar shape in mouse migratory neurons through LPA receptor 4 (LPA4). LPA4 is robustly expressed in migratory neurons. LPA4-depleted neurons show impaired multipolar-to-bipolar transition and become arrested in their migration. Further, LPA4-mediated LPA signaling promotes formation of the pia-directed process in primary neurons overlaid on neocortical slices. In addition, LPA4 depletion is coupled with altered actin organization as well as with destabilization of the F-actin-binding protein filamin A (FlnA). Finally, overexpression of FlnA rescues the morphology and migration defects of LPA4-depleted neurons. Thus, the LPA-LPA4 axis regulates bipolar morphogenesis and radial migration of newborn cortical neurons via remodeling of the actin cytoskeleton.