Neurotransmitter diversity in pre‐synaptic terminals located in the parvicellular neuroendocrine paraventricular nucleus of the rat and mouse hypothalamus

• Published in: Journal of comparative neurology (1911) 2018-06, Vol.526 (8), p.1287-1306
• Main Authors: Johnson, Caroline S., Bains, Jaideep S., Watts, Alan G.
• Format: Article
• Language: English
• Subjects: Adrenal glands; catecholamine; Catecholamines; Corticotropin-releasing hormone; Dopamine transporter; Dopamine β-monooxygenase; Epinephrine; GABA; glutamate; Glutamic acid transporter; Hydroxylase; Hypothalamus; Immunohistochemistry; Methyltransferase; Neuromodulation; Neurons; Neurotransmitters; Norepinephrine; Paraventricular nucleus; pre‐motor; Rodents; RRID:AB_1587626; RRID:AB_2187832; RRID:AB_2198864; RRID:AB_2236176; RRID:AB_2245740; RRID:AB_2313908; RRID:AB_2315181; RRID:AB_572229; RRID:AB_887871; RRID:RGD_737903; RRID:SCR_002668; Synaptophysin; Transgenic mice
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24407

Virtually all rodent neuroendocrine corticotropin‐releasing‐hormone (CRH) neurons are in the dorsal medial parvicellular (mpd) part of the paraventricular nucleus of the hypothalamus (PVH). They form the final common pathway for adrenocortical stress responses. Their activity is controlled by sets of GABA‐, glutamate‐, and catecholamine‐containing inputs arranged in an interactive pre‐motor network. Defining the nature and arrangement of these inputs can help clarify how stressor type and intensity information is conveyed to neuroendocrine neurons. Here we use immunohistochemistry with high‐resolution 3‐dimensional image analyses to examine the arrangement of single‐ and co‐occurring GABA, glutamate, and catecholamine markers in synaptophysin‐defined pre‐synaptic terminals in the PVHmpd of unstressed rats and Crh‐IRES‐Cre;Ai14 transgenic mice: respectively, vesicular glutamate transporter 2 (VGluT2), vesicular GABA transporter (VGAT), dopamine β‐hydroxylase (DBH), and phenylethanolamine n‐methyltransferase (PNMT). Just over half of all PVHmpd pre‐synaptic terminals contain VGAT, with slightly less containing VGluT2. The vast majority of terminal appositions with mouse CRH neurons occur non‐somatically. However, there are significantly more somatic VGAT than VGluT2 appositions. In the rat PVHmpd, about five times as many pre‐synaptic terminals contain PNMT than DBH only. However, because epinephrine release has never been detected in the PVH, PNMT terminals may functionally be noradrenergic not adrenergic. PNMT and VGluT2 co‐occur in some pre‐synaptic terminals indicating the potential for co‐transmission of glutamate and norepinephrine. Collectively, these results provide a structural basis for how GABA/glutamate/catecholamine interactions enable adrenocortical responses to fast‐onset interosensory stimuli, and more broadly, how combinations of PVH neurotransmitters and neuromodulators interact dynamically to control adrenocortical activity. The activity of neuroendocrine neurons in the paraventricular nucleus of the hypothalamus (PVH) is controlled by sets of pre‐motor inputs. Using immunohistochemistry and confocal image analysis we examine single and co‐occurrence of catecholaminergic, glutamatergic, and GABAergic markers in synaptophysin‐defined axon terminals in the PVH region that mostly contains CRH neurons. We provide a structural basis for how these transmitter interactions enable adrenocortical responses to fast‐onset interosensory stimuli, and m