Microiontophoretic studies of thalamic neurons suggests that nitric oxide (
NO) plays an important role in mediating somatosensory transmission. The th
alamus contains few nitric oxide synthase (NOS)-immunoreactive neurons; thu
s, the major source of thalamic NO is presumably from NOS-positive axons of
extrathalamic origin. The cells of origin of these putative NOS-containing
pathways to the ventrobasal thalamus were investigated in rats by combinin
g retrograde tracing with immunocytochemistry for NOS. The location and mor
phology of double-labeled neurons was compared with that of single-labeled
neurons. The most significant sources of NOS-containing afferents to the th
alamus were found to be the pedunculopontine (PPN) and laterodorsal tegment
al (LDT) nuclei. NOS-immunoreactive neurons in these cholinergic nuclei pro
ject bilaterally to the thalamus, most strongly ipsilaterally. The thalamus
appears to be a major target of PPN, since even selective thalamic injecti
ons result in retrograde labeling of at least one third of its NOS-immunore
active neurons. A significant number of NOS-negative neurons in both the PP
N and LDT also project to the thalamus. Minor sources of NOS-containing tha
lamic afferents include the lateral hypothalamus, the dorsal, median and po
ntine raphe nuclei, the parabrachial nuclei, and the pontomedullary reticul
ar formation. In all these structures, NOS-negative thalamopetal neurons gr
eatly outnumber the NOS-positive ones. Ascending sensory pathways to the th
alamus, including those from the sensory trigeminal nuclei, the dorsal colu
mn nuclei, and the spinal cord, as well as the auditory and vestibular cent
ers, arise exclusively from NOS-negative neurons. The major NOS-positive pr
ojections are implicated in affective and alerting systems, supporting that
NO may act to modulate attentiveness in thalamic relay nuclei.