GLUTAMATE AND GABAERGIC NEUROINTERACTIONS IN THE MONKEY HYPOTHALAMUS - A QUANTITATIVE IMMUNOMORPHOLOGICAL STUDY

Glutamate (Glu) and gamma-aminobutyric acid (GABA) are the most abunda nt excitatory and inhibitory neurotransmitters in the mammalian hypoth alamus. Glu and GABA-containing neurons have both been shown to synaps e with gonadotropin-releasing hormone (GnRH) and other neuroendocrine systems in the hypothalamus of several species. Since their direct int eractions could play a pivotal role in governing neuroendocrine functi on, we performed double-label immunostaining for Glu and for glutamic acid decarboxylase (GAD) as a marker for GABAergic neurons in hypothal amic sections from adult female cynomolgus monkeys. Ultrastructural an alysis of 785 Glu-immunoreactive (-ir) and GAD-ir elements in the medi al septum (MS), arcuate nucleus-ventral hypothalamic tract (VHT1), sup raoptic nucleus (SON), paraventricular nucleus (PVN), and median emine nce (ME) revealed that 63% were Glu-ir, 28% were GAD-ir, and 9%, were Glu+GAD-ir. In addition, we observed surprisingly consistent labeling of 2-4% somata (SOM), 65-80% dendrites (DEN), and 15-30% axons and ter minals (AXO) in all of these areas. Characterization of 177 interactio ns (36% synapses, 64% contacts) by pre-/post-transmitter content indic ated that 29% contained Glu/GAD, 15% Glu/Glu, and 15% Glu/Glu+GAD, whi le 16% were unlabeled/Glu, 9% were unlabeled/GAD, and 16% expressed ot her transmitter combinations. Regional analysis of these interactions showed that 43% occurred in the MS, 22% in VHT1, 14% in SON, 9% in PVN , and 12% in the ME. AXO/DEN interactions made up 51% of all labeled i nteractions characterized, and were comprised 29% of Glu/GAD, 22% of G lu/Glu, and 18% of the Glu/Glu+GAD type. AXO/DEN synapses were more pr evalent than contacts in all areas except the PVN and of course the ME , where anatomical synapses do not occur. AXO/SOM interactions represe nted approximately 15% of all those identified, and were predominantly unlabeled/Glu (71%) and unlabeled/GAD (18%) synapses. Almost all (95% ) AXO/SOM synapses and 75% of the contacts occurred in the MS. DEN/DEN interactions, 28% of the total, were composed 50% of Glu/GAD, 12% of Glu/Glu, and 18% of the Glu/Glu+GAD type. The relatively few DEN/DEN s ynapses all appeared in the MS, whereas much more abundant DEN/DEN con tacts were more widely distributed. DEN/SOM interactions, 6% of the to tal, appeared only as contacts, with the majority (60%) again located in the MS. In addition, the MS contained 48% of all asymmetrical synap ses (vs. 35% in VHT1 and 17% in SON), 62% of all symmetrical synapses (vs. 19% in VHT1 and 14% in SON), and 35% of all contacts (vs. 21% in VHT1 and 12% in SON) identified. In summary, Glu-ir neuronal processes are about twice as numerous as GAD-ir elements in the female monkey h ypothalamus. Glu-ir afferents are found in nearly 2/3 of these contact s, participating in classical synapses, novel specializations, and int imate local circuits. Interactions occur principally in the MS, VHT1, and to a lesser extent in the SON, PVN, and ME, all of which are impor tant sites of neuroendocrine integration. On the basis of our past and present data, we propose a model of Glu-GABA-GnRH neurointeractions w hich may help mediate GnRH secretion in the monkey hypothalamus.