Evidence that cholinergic axons from the parabrachial region of the brainstem are the exclusive source of nitric oxide in the lateral geniculate nucleus of the cat

Abstract

We investigated the source of axons and terminals in the cat's lateral geniculate nucleus that stain positively for NADPH-diaphorase. The functional significance of such staining is that NADPH-diaphorase is identical to the enzyme nitric oxide synthetase, and thus it is thought to reveal cells and axons that use nitric oxide as a neuromodulator. Within the lateral geniculate and adjacent perigeniculate nuclei, a dense network of axons and terminals is labeled for NADPH-diaphorase. The pattern of NADPH-diaphorase staining here is remarkably similar to that of choline acetyltransferase (ChAT) staining, suggesting that the source of these axons and terminals might be the parabrachial region of the brainstem because this provides the major cholinergic input to the lateral geniculate nucleus. In other areas of the brain to which parabrachial axons project, there is also a similar staining pattern for NADPH-diaphorase and ChAT. Furthermore, the patterns of cell staining within the parabrachial region for NADPH-diaphorase and ChAT are virtually identical. However, the relationship between ChAT and NADPH-diaphorase staining for the parabrachial region is not a general property of cholinergic neurons. Other cholinergic cells and axons, such as the trochlear nerve, the oculomotor nerve and nucleus, and the parabigeminal nucleus, which all label densely for ChAT, stain poorly or not at all for NADPH-diaphorase. It is significant that the parabigeminal nucleus, which provides a cholinergic input to the lateral geniculate nucleus, has no cells that label for NADPH-diaphorase. We used double labeling methods to identify further the source of NADPH-diaphorase staining in the lateral geniculate nucleus. We found that parabrachial cells co-localize NADPH-diaphorase and ChAT. Noradrenergic and serotoninergic cells in the brainstem also innervate the lateral geniculate nucleus, but we found that none of these co-localize NADPH-diaphorase. Finally, by combining NADPH-diaphorase histochemistry with retrograde labeling of cells that project to the lateral geniculate nucleus, we found that the cholinergic cells of the parabrachial region are essentially the sole source of NADPH-diaphorase in the lateral geniculate nucleus. We thus conclude that cells from the parabrachial region that innervate the lateral geniculate nucleus use both acetylcholine and nitric oxide for neurotransmission, and that this is virtually the only afferent input to this region that uses nitric oxide.

Monoamines and nitric oxide are employed by afferents engaged in midline thalamic regulation

“…The aforementioned data suggest that the n.Pvt constitutes one of the principal targets in the midline-intralaminar complex of afferents presumed to generate NO. NO in the lateral geniculate body derives exclusively from neurons that cosynthesize ACh (Bickford et al, 1993). The following observations, however, indicate that the principal source of mesopontine afferent projection to the n.Pvt is noncholinergic.…”

“…The functional significance of the dense monoaminergic and NADPH-d positive plexi in the n.Pvt and striking spatial overlap with cholinergic processes in the central media1 intralaminar nucleus is unknown. We can predict, based on our structural data, that interactions attributed to the mesopontine source of NO in the LGN (P-ape and Mager, 1992;Bickford et al, 1993) may also apply to actions on nonspecific thalamosensory neurons in the midline-intralaminar complex.…”

“…Myriad afferents to the thalamus have been identified including neurons which synthesize GABA (Montero and Zempel, 1985;Montero, 1987;Asanuma and Porter, 1990), monoamines (Swanson and Hartman, 1975;Consolazione et al, 1984;Westlund et al, 1990;Asanuma, 1992;Sim and Joseph, 1992), and ACh (Asanuma, 1989;Hallanger et al, 1987;Steriade et al, 1987), and, as recently suggested, a nitric oxide (NO) synthase (Bickford et al, 1993). The origins and postsynaptic targets of most chemically identified processes within the midline thalamus, however, have not been explored.…”

A Role for Nitric Oxide in the Development of the Ferret Retinogeniculate Projection

“…Although NADPH-diaphorase staining is developmentally regulated in LGN cells, staining is present in the neuropil in the LGN at all ages . Neuropil staining arises from cholinergic brainstem projections (Bickford et al, 1993). Because blockade of NOS at early ages does not interfere with the formation of eye-specific layers, it is unlikely that NO produced in the neuropil is involved in early retinogeniculate pattern formation.…”

Distribution of NADPH-Diaphorase-Positive Neurons in the Mouse Brain: Differences from Previous Findings in the Rat Brain and Comparison with the Distribution of Serotonergic Neurons.

“…Within the ventrolateral geniculate nucleus, a dense network of axons and terminals was revealed by staining for NADPH-d in this study. Bickford et al [2] found that parabrachial cells were co-localizd with NADPH-d and ChAT, and the cholinergic cells of the parabrachial region are essentially the sole source of NADPH-d in the lateral geniculate nucleus. They also reported that NADPH-d-positive cells in the parabrachial region were not labeled for 5-HT.…”