Brain Structure and Function

, Volume 216, Issue 4, pp 331–345

Projections from the rat pedunculopontine and laterodorsal tegmental nuclei to the anterior thalamus and ventral tegmental area arise from largely separate populations of neurons

Original Article

DOI: 10.1007/s00429-011-0320-2

Cite this article as:
Holmstrand, E.C. & Sesack, S.R. Brain Struct Funct (2011) 216: 331. doi:10.1007/s00429-011-0320-2


Cholinergic and non-cholinergic neurons in the brainstem pedunculopontine (PPT) and laterodorsal tegmental (LDT) nuclei innervate diverse forebrain structures. The cholinergic neurons within these regions send heavy projections to thalamic nuclei and provide modulatory input as well to midbrain dopamine cells in the ventral tegmental area (VTA). Cholinergic PPT/LDT neurons are known to send collateralized projections to thalamic and non-thalamic targets, and previous studies have shown that many of the afferents to the VTA arise from neurons that also project to midline and intralaminar thalamic nuclei. However, whether cholinergic projections to the VTA and anterior thalamus (AT) are similarly collateralized is unknown. Ultrastructural work from our laboratory has demonstrated that cholinergic axon varicosities in these regions differ both morphologically and with respect to the expression and localization of the high-affinity choline transporter. We therefore hypothesized that the cholinergic innervation to these regions is provided by separate sets of PPT/LDT neurons. Dual retrograde tract-tracing from the AT and VTA indicated that only a small percentage of the total afferent population to either region showed evidence of providing collateralized input to the other target. Cholinergic and non-cholinergic cells displayed a similarly low percentage of collateralization. These results are contrasted to a control case in which retrograde labeling from the midline paratenial thalamic nucleus and the VTA resulted in higher percentages of cholinergic and non-cholinergic dual-tracer labeled cells. Our results indicate that functionally distinct limbic target regions receive primarily segregated signaling from PPT/LDT neurons.


Acetylcholine Limbic circuitry Collateral Brainstem Midbrain Dopamine 

Supplementary material

429_2011_320_MOESM1_ESM.tif (21.6 mb)
Online Resource 1 Montage of three-channel fluorescence images through the PPT of Case 37 demonstrates the intermingling of AT-projecting and VTA-projecting neurons within this nucleus. For each individual field, multiple focal planes were used to create a three dimensional projection in Image J that was subsequently flattened to display all the labeled neurons as if they lay within a single plane. These flattened images were then aligned to show the distribution of cells throughout the PPT at this particular rostrocaudal level. Similar to the schematic presented in Fig. 6, the lack of gross segregation of AT- and VTA-projecting neurons can be appreciated in this region. Additionally, by downloading the figure and manipulating the display of individual fluorescence channels, the specific combinations of labeling may be confirmed. Scale bar equals 100 μm. Abbreviations: scp, superior cerebellar peduncle. (TIFF 22113 kb)
429_2011_320_MOESM2_ESM.tif (28.9 mb)
Online Resource 2 Montage of three-channel fluorescence images through the dorsal LDT of Case 37 demonstrating the intermingling of AT-projecting and VTA-projecting neurons within this nucleus. Image creation was the same as for Online Resource 1. Scale bar equals 200 μm. Abbreviations: dtg, dorsal tegmental nucleus of Gudden; 4 V, fourth ventricle; mlf; medial longitudinal fasciculus. (TIFF 29549 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of NeuroscienceUniversity of PittsburghPittsburghUSA
  2. 2.Department of PsychiatryUniversity of PittsburghPittsburghUSA
  3. 3.Department of PharmacologyVanderbilt UniversityNashvilleUSA