Topographical organization of the pedunculopontine nucleus

Abstract

Neurons in the pedunculopontine nucleus (PPN) exhibit a wide heterogeneity in terms of their neurochemical nature, their discharge properties, and their connectivity. Such characteristics are reflected in their functional properties and the behaviors in which they are involved, ranging from motor to cognitive functions, and the regulation of brain states. A clue to understand this functional versatility arises from the internal organization of the PPN. Thus, two main areas of the PPN have been described, the rostral and the caudal, which display remarkable differences in terms of the distribution of neurons with similar phenotype and the projections that originate from them. Here we review these differences with the premise that in order to understand the function of the PPN it is necessary to understand its intricate connectivity. We support the case that the PPN should not be considered as a homogeneous structure and conclude that the differences between rostral and caudal PPN, along with their intrinsic connectivity, may underlie the basis of its complexity.

Keywords: basal ganglia; brainstem; connectivity; microcircuits; neuronal heterogeneity; pedunculopontine; reticular activating system; synaptic organization.

Figure 1

Schematic representation of the distribution of distinct neuronal populations in the PPN. GABAergic neurons are highly concentrated in the rostral PPN, whereas cholinergic, glutamatergic (not shown), calbindin- and calretinin-expressing neurons are more abundant in the caudal PPN. The PPN was divided into 300 μm segments and cell density was evaluated throughout its rostro-caudal extent (Martinez-Gonzalez et al., ; Mena-Segovia et al., 2009). The difference in the rostro-caudal distribution of GABAergic neurons correlates with the differences in cytoarchitecture of the cholinergic neurons traditionally used to identify PPN regions (i.e., pars dissipata and pars compacta). As shown in this figure, the rostral PPN is an area of high neuronal density. SN, substantia nigra.

Figure 2

Summary of the topographical distribution of the connectivity in the PPN. The rostral PPN, which is predominantly GABAergic, maintains interconnections with the GABAergic output of the basal ganglia. In contrast, the caudal PPN, where cholinergic and glutamatergic neurons are more abundant, receives input from the cortex and dorsal raphé and projects to the thalamocortical systems, STN and locomotor regions. Only major inputs and outputs, and those structures whose connectivity with the PPN is topographically organized, are depicted in this scheme. EP, entopeduncular nucleus; GPi, internal segment of the globus pallidus; IC, inferior colliculus; SC, superior colliculus; SN, substantia nigra; STN, subthalamic nucleus; VTA, ventral tegmental area.