Dual-Phenotype GABA/Glutamate Neurons in Adult Preoptic Area: Sexual Dimorphism and Function

Abstract

It is generally assumed that the inhibitory neurotransmitter GABA and the stimulatory neurotransmitter glutamate are released from different neurons in adults. However, this tenet has made it difficult to explain how the same afferent signals can cause opposite changes in GABA and glutamate release. Such reciprocal release is a central mechanism in the neural control of many physiological processes including activation of gonadotropin-releasing hormone (GnRH) neurons, the neural signal for ovulation. Activation of GnRH neurons requires simultaneous suppression of GABA and stimulation of glutamate release, each of which occurs in response to a daily photoperiodic signal, but only in the presence of estradiol (E 2 ). In rodents, E 2 and photoperiodic signals converge in the anteroventral periventricular nucleus (AVPV), but it is unclear how these signals differentially regulate GABA and glutamate secretion. We now report that nearly all neurons in the AVPV of female rats express both vesicular glutamate transporter 2 (VGLUT2), a marker of hypothalamic glutamatergic neurons, as well as glutamic acid decarboxylase and vesicular GABA transporter (VGAT), markers of GABAergic neurons. These dual-phenotype neurons are the main targets of E 2 in the region and are more than twice as numerous in females as in males. Moreover, dual-phenotype synaptic terminals contact GnRH neurons, and at the time of the surge, VGAT-containing vesicles decrease and VGLUT2-containing vesicles increase in these terminals. Thus, we propose a new model for ovulation that includes dual-phenotype GABA/glutamate neurons as central transducers of hormonal and neural signals to GnRH neurons.

GABAergic Neurons in the Central Region of the Spinal Cord: A Novel Substrate for Sympathetic Inhibition

“…1 Aii-Dii). Although GAD 67 is coexpressed with vesicular glutamate transporter 2 in some neurons (e.g., the preoptic area) (Ottem et al, 2004), this is an unusual occurrence not reported in the spinal cord. Furthermore, the location of GAD-expressing neurons correlates with the source of GABAergic inhibition in SPNs revealed here (see below).…”

Endogenous Activation of Metabotropic Glutamate Receptors Modulates GABAergic Transmission to Gonadotropin-Releasing Hormone Neurons and Alters Their Firing Rate: A Possible Local Feedback Circuit

“…Although not released by most GABAergic terminals (Somogyi et al, 1986), glutamate is a precursor for GABA synthesis. In some cases, both GABA and glutamate are stored by the same terminals (Sandler and Smith, 1991;Somogyi, 2002;Ottem et al, 2004) and may be coreleased. Finally, postsynaptic dendrites may release glutamate or other transmitters specifically to the presynaptic terminals (Zilberter, 2000).…”

The Median Preoptic Nucleus Reciprocally Modulates Activity of Arousal-Related and Sleep-Related Neurons in the Perifornical Lateral Hypothalamus

“…Excitation of MCH cells rather than disinhibition (Goutagny et al, 2005;Modirrousta et al, 2005) seems to play a critical role in their sleep-related activation, because in vitro MCH neurons are virtually silent (Eggermann et al, 2003;van den Pol et al, 2004;Bayer et al, 2005 (Gong et al, 2004;Gvilia et al, 2005). We hypothesize that MnPN sleep-promoting neuronal population is either cytochemically heterogeneous (includes both GABAergic neurons and excitatory cells with unknown neurotransmitter phenotype) or contains neurons that colocalize excitatory and inhibitory neurotransmitters as occurs in dual phenotype GABA/glutamate cells in adjacent anteroventral periventricular nucleus (Ottem et al, 2004).…”