Corticotropin-releasing factor is preferentially colocalized with excitatory rather than inhibitory amino acids in axon terminals in the peri-locus coeruleus region

Corticotropin-releasing factor(CRF)-immunoreactive terminals form synaptic specializations with locus coeruleus (LC) dendrites in rat brain. Within th ese terminals, CRF-immunoreactive dense core vesicles are colocalized with non-labeled dense core vesicles and clear vesicles, implicating other neuro modulators in the actions of CRF on LC neurons. Excitatory (glutamate) and inhibitory (GABA) amino acid afferents to the LC, have been identified whic h regulate noradrenergic responses to sensory stimuli. This study was desig ned to determine whether these amino acid neurotransmitters are colocalized with CRF in terminals within the LC/peri-LC region in the rat. Sections th rough the LC region that were dually labeled using immunohistochemical tech niques to visualize either CRF and glutamate or CRF and GABA were examined using electron microscopy. Numerous terminals that contained immunolabeling for both CRF and glutamate (e.g. 30% of 106 CRF-immunoreactive terminals and 13% of 232 glutamate-imm unolabeled terminals) were observed in the peri-LC. Additionally, single la beled CRF and glutamate terminals were often apposed to one another or foun d to converge on common dendritic targets. In contrast, relatively few term inals exhibited immunolabeling for both GABA and CRF (5% of 317 CRF-immunor eactive terminals). However, evidence for a postsynaptic effect of CRF on G ABA-containing profiles included synapses between CRF axon terminals and GA BA-labeled dendrites (10% of 317 CRF-labeled terminals), as well as apposit ions between CRF- and GABA-labeled terminals. These results indicate that CRF is preferentially colocalized with glutamat e in the rostrolateral LC region and may impact on glutamate neuro transmis sion in the LC via presynaptic or postsynaptic actions. They argue against colocalization of CRF with GABA, although CRF may modulate GABA release via postsynaptic effects in the peri-LC region. (C) 2001 IBRO. Published by El sevier Science Ltd. All rights reserved.