title: Area-specific analysis of the distribution of hypothalamic neurons projecting to the rat ventral tegmental area, with special reference to the GABAergic and glutamatergic efferents.
abstract: The ventral tegmental area (VTA) is a main regulator of reward and integrates a wide scale of hormonal and neuronal information. Feeding-, energy expenditure-, stress, adaptation- and reproduction-related hypothalamic signals are processed in the VTA and influence the reward processes. However, the neuroanatomical origin and chemical phenotype of neurons mediating these signals to the VTA have not been fully characterized. In this study we have systematically mapped hypothalamic neurons that project to the VTA using the retrograde tracer Choleratoxin B subunit (CTB) and analyzed their putative gamma-aminobutyric acid (GABA) and/or glutamate character with in situ hybridization in male rats. 23.93 ± 3.91% of hypothalamic neurons projecting to the VTA was found in preoptic and 76.27 ± 4.88% in anterior, tuberal and mammillary hypothalamic regions. Nearly half of the retrogradely-labeled neurons in the preoptic, and more than one third in the anterior, tuberal and mammillary hypothalamus appeared in medially located regions. The analyses of vesicular glutamate transporter 2 (VGLUT2) and glutamate decarboxylase 65 (GAD65) mRNA expression revealed both amino acid markers in different subsets of retrogradely-labeled hypothalamic neurons, typically with the predominance of the glutamatergic marker VGLUT2. About one tenth of CTB-IR neurons were GAD65-positive even in hypothalamic nuclei expressing primarily VGLUT2. Some regions were populated mostly by GAD65 mRNA-containing retrogradely-labeled neurons. These included the perifornical part of the lateral hypothalamus where 58.63 ± 19.04% of CTB-IR neurons were GABAergic. These results indicate that both the medial and lateral nuclear compartments of the hypothalamus provide substantial input to the VTA. Furthermore, colocalization studies revealed that these projections not only use glutamate but also GABA for neurotransmission. These GABAergic afferents may underlie important inhibitory mechanism to fine-tune the reward value of specific signals in the VTA.
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary ; Faculty of Information Technology and Bionics, Pázmány Péter Catholic University Budapest, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Kalló
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Csilla S
authors.initials: CS
authors.lastname: Molnár
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Sarolta
authors.initials: S
authors.lastname: Szöke
authors.affiliation: Laboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary ; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center Boston, MA, USA.
authors.forename: Csaba
authors.initials: C
authors.lastname: Fekete
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Erik
authors.initials: E
authors.lastname: Hrabovszky
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary ; Faculty of Information Technology and Bionics, Pázmány Péter Catholic University Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Liposits
keywords: GABA; VTA; glutamate; hypothalamus; immunohistochemistry; in situ hybridization; preoptic area; retrograde labeling