Corticotropin-Releasing Factor Neurons Innervate Dopamine Neurons in the Periventricular Hypothalamus of Juvenile Macaques

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Abstract
Corticotropin-releasing factor (CRF) and dopamine (DA) are important integrators of the endocrine and autonomic response to stress. CRF neurons in the anterior portions of the periventricular nucleus (PV) and parvocellular paraventricular nucleus (pvPVN) occur close to A14 DA neurons in these same locations. Since CRF has been shown to act as an excitatory neurotransmitter, possible CRF interactions with the DA system were investigated using double-label immunocytochemistry. Coronal vibratome sections through the PV and pvPVN were obtained from colchicine-treated and nontreated juvenile female cynomolgus macaques. They were sequentially immunostained for tyrosine hydroxylase (TH) (to identify DA neurons) with PAP and DAB, and for CRF using 15 nm colloidal gold. By light microscopy, areas of coincidence of TH- and CRF-immunoreactive cell bodies in the PV and pvPVN were obvious, but double-stained elements were not observed. By electron microscopy, asymmetrical synapses frequently occured between CRF axons and TH dendrites or somata. Symmetrical axosomatic synapses sometimes appeared adjacent to these CRF/TH synapses, while symmetrical axoaxonic synapses were rare. We conclude that CRF neuronal efferents synaptically activate A14 DA neurons in the primate PV and pvPVN. Parallel CRF/DA symmetrical synapses also suggest coexistence of a companion transmitter within some of these same CRF neurons. Our own previous work and recent independent studies indicate that this transmitter is probably GABA. Thus the CRF neuronal system, which is known to alter secretion of several pituitary hormones, may also act through hypothalamic periventricular DA neurons to mediate other responses to stress.

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