The anterior pretectal nucleus (APT) and the zona incerta (ZI) are diencephalic nuclei
that exert a strong inhibitory influence selectively in higher order thalamic relays.
The APT is also known to project to the ZI as well as the thalamus, but anatomical
details of the APT-ZI projection have not been described. In the present study, the
efferent pathways of the APT were examined in the APT-ZI-thalamus network by using
anterograde and retrograde tracing in combination with pre- and postembedding immunocytochemical
stainings and in situ hybridization. The vast majority of APT fibers selectively innervated
the parvalbumin-positive, ventral part of the ZI, which contains ZI neurons with axons
projecting to higher order thalamic nuclei. The APT-ZI pathway consisted of both gamma-aminobutyric
acid (GABA)-negative and GABA-positive components; 38.2% of the terminals in the ZI
contained GABA, and 8.6% of the projecting somata in the APT were glutamic acid decarboxylase
67 (GAD67) mRNA positive. The combination of parvalbumin immunostaining with retrograde
tracing showed that strongly and weakly parvalbumin-positive as well as parvalbumin-negative
neurons were all among the population of APT cells projecting to the ZI. Similar heterogeneity
was found among the APT cells projecting to the thalamus. Double retrograde tracing
from higher order thalamic nuclei and their topographically matched ZI regions revealed
hardly any APT neuron with dual projections. Our data suggest that both ZI and the
higher order thalamic relays are innervated by distinct, physiologically heterogeneous
APT neurons. These various efferent pathways probably interact via the rich recurrent
collaterals of the projecting APT cells. Therefore, the powerful, GABAergic APT and
ZI outputs to the thalamus are apparently co-modulated in a synergistic manner via
dual excitatory and inhibitory APT-ZI connections. J. Comp. Neurol. 506:122-140, 2008.
(c) 2007 Wiley-Liss, Inc.
