Gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve cells have intrinsic rhythmicity and project widely in the brain

Abstract

Modulation of ionic channel properties and synaptic functions by neurotransmitters and hormones is called neuro-modulation and may be the basis for many long-lasting changes in animal behavior, for example, changes in the arousal or motivational states. We have previously shown in a teleost, the dwarf gourami, that the terminal nerve (TN) cells are a major component of the gonadotropin-releasing hormone (GnRH) system and are structurally independent from the preoptic/hypophysial-GnRH system, which projects to the pituitary and facilitates gonadotropin release from the gonadotropes. While GnRH fibers originating from TN cells are distributed widely throughout the brain, they do not project to the pituitary. Thus, TN-GnRH system does not function as a hypophysiotropic hormone but probably as a neuro-modulator, capable of affecting widespread regions of the brain. In the present study, we used a whole-brain in vitro preparation to examine the spontaneous electrical activities of TN-GnRH cells and to determine the morphology of individual cells by intracellular injections of either neurobiotin or biocytin. The recorded cells were clearly identified as GnRH-immunoreactive TN cells by using combined intracellular injection and GnRH immunocytochemistry. Most of the TN cells showed endogenous slow (1-7 Hz), regular beating discharges. The intrinsic nature of this activity was demonstrated by the voltage dependency of the beating frequency, rhythm resetting, and persistence of rhythmicity after synaptic isolation. Only a small number of TN cells showed either irregular or bursting discharge patterns. Anatomical observation of intracellularly labeled cells showed that, regardless of discharge patterns, all the TN cells had multiple axonal branches that project to those areas where we had previously demonstrated dense GnRH-immunoreactive fibers. From the present results, we propose a hypothesis that may be relevant to the peptidergic and monoaminergic neuromodulatory systems in general. The modulator neurons have endogenous rhythmic activities that vary according to the animal's hormonal or environmental conditions, and they regulate the excitability of target neurons in a wide variety of brain regions simultaneously via multiple axonal branches.

The GnRH system in the European sea bass (Dicentrarchus labrax)

“…However, the present results also indicate a minor contribution of sGnRH fibers to the pituitary, although the precise origin of these projections remains to be established. In the dwarf gourami, the terminal nerve ganglion cells have been shown to project widely in the brain, but not in the pituitary (Oka & Matsushima 1993). It is generally believed that GnRH-immunoreactive cells of the terminal nerve are not essential for the regulation of gonadotropin release, an assumption strongly reinforced by the fact that sectioning the olfactory tract in female goldfish does not impair gonadal development and ovulation (Kobayashi et al 1994).…”

Neuromodulatory Effect of GnRH on the Synaptic Transmission of the Olfactory Bulbar Neural Circuit in Goldfish, Carassius auratus

“…So far, it has been suggested that TNGnRH neurons show regular pacemaker activities (Fujita et al 1991;Oka and Matsushima 1993;Ramakrishnan and Wayne 2009;Wayne et al 2005) and GnRH release is evoked by depolarizing stimulus that increases the firing frequency of these neurons (Abe and Oka 2007;Ishizaki et al 2004). Considering that TN cell bodies appear to receive direct and indirect inputs from multimodal sensory systems (Fujita et al 1985(Fujita et al , 1991Ramakrishnan and Wayne 2009; Ito 2000), GnRH should be released from TN depending on these sensory inputs.…”

“…There are some reports that GnRH has neuromodulatory effects on the sensory responsiveness of animals (Abe and Oka 2007;Eisthen et al 2000;Kawai et al 2009b;Oka 1997;Oka and Matsushima 1993;Park and Eisthen 2003;Umino and Dowling 1991). In mudpuppies (Necturus maculosus), for example, GnRH increases the amplitude of a tetrodotoxinsensitive inward current in the olfactory receptor neurons (Eisthen et al 2000), suggesting that GnRH increases the excitability of these neurons.…”

Reproductive Biology of Salmoniform and Pleuronectiform Fishes with Special Reference to Gonadotropin-Releasing Hormone (GnRH)

“…Despite large decreases in the brain sGnRH contents, gonadal maturation was not inhibited (Kobayashi et al , 1994Kim et al 2001). In dwarf gourami, sGnRH neurons in the TN may be the most extensively projecting GnRH neurons in the brain except in the pituitary (Oka and Matsushima 1993). These results indicate that most of the sGnRH fibers in the brain originates from the TN and that sGnRH neurons in the TN do not project to the pituitary.…”