Plasticity of catecholaminergic terminals in rat paraventicular hypothalamic nucleus after 6-Hydroxydopamine lesion: an emphasis on bouton sizes and synaptic frequency

Abstract

Catecholaminergic (CA) nerve terminals in the paraventicular hypothalamic nucleus (PVN) of adult rats were studied at 4, 21, 56 and 180 days after a single injection of 6-hydroxydopamine (6-OHDA) neurotoxin into the right lateral ventricle of the brain. We previously described and quantified the extent of CA terminal sprouting in the PVN after 6-OHDA lesions. For this communication we studied parameters, specifically the bouton sizes and the synaptic frequencies of CA terminals during the renewal process, and evaluated how changes of these parameters are ralated to axonal sprouting. The CA boutons were identifiable in the electron microscope by exhibiting small granular vesicle (SGVs) after central administration of 5-hydroxydopamine (5-OHDA) marker. The marked CA boutons were measured and further categorized according to whether or not they were associated with distinct synaptic specializations at various post-lesion stages. The average sizes of CA boutons were strikingly similar in their diameters (1.0 υm) for both control and experimental tissues. However, CA boutons larger than 2.1 υm were rare and seen more often in the experimental tissues with 6-OHDA lesion and were sustained up to 180 days after lesions. Catecholaminergic profiles with ultrastructural features of growth cones were also seen in the PVN following the 6-OHDA lesions, indicating that there is growth activity in the PVN after 6-OHDA lesion. There were 33% of CA boutons in the PVN from the control tissues that appeared to have contacts. Four days after lesions with a significant reduction of CA terminals, the synaptic frequency was seen on 31% of surviving CA terminals; this synaptic frequency (31%) is close to that observed before lesioning. Of the CA boutons, 42% possessed synaptic contacts at both 21 and 56 days postlesion. At these stages there is still limited regeneration of CA terminals. At 180 days afler lesions with a significant CA terminal restoration, the synaptic frequency of CA boutons had dropped to 36%, a value closer to the control level. The following conclusions can be drawn: (1) the synaptic frequency of CA terminals 4 days afler lesions resembles that of controls, suggesting that synaptic contacts found at this short survival period are those CA terminals escaped from 6-OHDA destruction, not from regenerating fibers; (2) a higher synaptic frequency was exhibited by CA terminals at 21 and 56 days after lesions; by 180 days after the lesion; a subsequent decrease of synaptic frequency was observed on CA terminals, indicating synaptic plasticity of CA terminals; and (3) CA stumps in the PNV are able to extend to establish their synaptic contacts at a frequency close to control levels by 180 days after 6-OHDA lesion, suggesting that regenerative fibers may be functional.