Anatomical and pharmacological relationship between acetylcholine and nitric oxide in the prepositus hypoglossi nucleus of the cat: Functional implications for eye‐movement control

Abstract

The prepositus hypoglossi (PH) nucleus has been proposed as a pivotal structure for horizontal eye-position generation in the oculomotor system. Recent studies have revealed that acetylcholine (ACh) in the PH nucleus could mediate the persistent activity necessary for this process, although the origin of this ACh remains unknown. It is also known that nitric oxide (NO) in the PH nucleus plays an important role in the control of velocity balance, being involved in a negative feedback control of tonic signals arriving at the PH nucleus. As it could be expected that neurons taking part in eye-position generation must control their tonic background inputs, the existence of a relationship between nitrergic and cholinergic neurons is hypothesized. In the present study we analyzed the distribution, size, and morphology of choline acetyltransferase-positive neurons, and their relationship with neuronal nitric oxide synthase in the PH nucleus of the cat. As presumed, some 96% of cholinergic neurons were also nitrergic in the PH nucleus, suggesting that NO is regulating the level of ACh released by cholinergic PH neurons. Furthermore, we studied the alterations induced by muscarinic-receptor agonists and antagonists on spontaneous and vestibularly induced eye movements in the alert cat and compared them with those induced in previous studies by modification of NO levels in the same animal preparation. The results suggest that ACh is necessary for the generation of saccadic and vestibular eye-position signals, whereas the NO is stabilizing the eye-position generator by controlling background activity reaching cholinergic neurons in the PH nucleus.

Co-localization of nitric oxide synthase and choline acetyltransferase in the brain of the goldfish (Carassius auratus)

“…In addition, it has been proposed that NO modulates the extraocular muscle contraction in mammals (Kaminski and Richmonds, 2002); the extension of such proposal to other vertebrates would require further research. Indeed, the high degree of co-localization of nNOS and ChAT cells reported here is a new description that could be interpreted in the frame that NO modulates the cholinergic system, as suggested in mammals (Má rquez-Ruiz et al, 2007). The Edinger-Westphal nucleus showed a high degree of co-localization of nNOS-and ChAT-labeled cells.…”

“…These data could imply that there is crosstalk between both enzymatic pathways. The co-distribution and/or co-localization of nNOS and ChAT has been studied in mammals (Kitchener and Diamond, 1993;Dun et al, 1994;Sugaya and McKinney, 1994;Personett et al, 2000;Scheiner et al, 2000;Varga et al, 2003;Má rquez-Ruiz et al, 2007), birds (Necker, 2004), reptiles (Mé dina et al, 2004), and amphibians (Muñ oz et al, 2000). According to these studies, nNOS and ChAT are co-distributed in certain brain nuclei.…”

“…According to these studies, nNOS and ChAT are co-distributed in certain brain nuclei. The percentage of double-labeled cells is low (Dun et al, 1994;Sugaya and McKinney, 1994;Varga et al, 2003) or high (Má rquez-Ruiz et al, 2007) depending on the investigated nuclei. Similar studies are lacking in fish.…”

Extraocular motoneurons of the adult rat show higher levels of vascular endothelial growth factor and its receptor Flk-1 than other cranial motoneurons

“…Again, no specific labeling was found (Fig 1C and 1F). We have previously described the specificity of ChAT [27] and VEGF [26] antibodies. The antibody used against Flk-1 receptor selectively detects the presence of this receptor in neurons, but not in endothelial cells [28].…”

Differential regulation of the expression of neurotrophin receptors in rat extraocular motoneurons after lesion

“…The antibody stained a single band of 68-70 kDa corresponding to the predicted molecular weight of ChAT on Western blot from rat tissue (Corcoran et al, 2004;Brunelli et al, 2005). Specificity has been previously demonstrated by using the blocking peptide (Márquez-Ruiz et al, 2007). All staining was abolished when the primary antibody was preincubated with 15 lg/ml of the blocking peptide (choline acetyltransferase, rat recombinant protein, Chemicon, cat.…”