The Cellular Diversity of the Pedunculopontine Nucleus: Relevance to Behavior in Health and Aspects of Parkinson’s Disease

Abstract

The pedunculopontine nucleus (PPN) is a rostral brainstem structure that has extensive connections with basal ganglia nuclei and the thalamus. Through these the PPN contributes to neural circuits that effect cortical and hippocampal activity. The PPN also has descending connections to nuclei of the pontine and medullary reticular formations, deep cerebellar nuclei, and the spinal cord. Interest in the PPN has increased dramatically since it was first suggested to be a novel target for treating patients with Parkinson's disease who are refractory to medication. However, application of frequency-specific electrical stimulation of the PPN has produced inconsistent results. A central reason for this is that the PPN is not a heterogeneous structure. In this article, we review current knowledge of the neurochemical identity and topographical distribution of neurons within the PPN of both humans and experimental animals, focusing on studies that used neuronally selective targeting strategies to ascertain how the neurochemical heterogeneity of the PPN relates to its diverse functions in relation to movement and cognitive processes. If the therapeutic potential of the PPN is to be realized, it is critical to understand the complex structure-function relationships that exist here.

Temporal-Spatial Profiling of Pedunculopontine Galanin-Cholinergic Neurons in the Lactacystin Rat Model of Parkinson’s Disease

“…Using this rat model of PD, our current findings indicate that galanin expression levels could play a potentially important role in determining clinical manifestations of PD that associate with PPN cholinergic neuronal death, which include motor dysfunctions (e.g. gait dysfunction) as well as neuropsychiatric disturbances, such as those affecting cognition (reviewed by Pienaar et al 2016). Thus far, studies focusing on galanin-ACh interactions have primarily done so within the context of AD.…”

“…The PPN is composed of a rich diversity of neuronal cell-types, with three major neurochemically distinct neuronal groups that have been identified in the PPN, namely cholinergic, GABA (gamma-aminobutyric acid)-ergic and glutamatergic neurons, which are heterogeneously distributed along its rostro-caudal axis (reviewer by Pienaar et al 2016). Glycine immunoreactivity was also reported to be present in the human PPN , as well as in various other vertebrate species (Fort et al 1993;Mineff et al 1998) neuropeptides.…”

Commentary: Activation of Pedunculopontine Glutamate Neurons Is Reinforcing

“…This simultaneous release of multiple neurotransmitters by the same neuron can enhance the spatial and temporal control of synaptic transmission. Molecular evidence also support co-expression of Choline acetyltransferase and GABA in PPTg cultures, putting further spin on the role of combined neurotransmitter release (Pienaar et al, 2016 ).…”

Targeting the pedunculopontine nucleus in Parkinson's disease: Time to go back to the drawing board

“…The PPN is a heterogeneous region composed of cholinergic, glutamatergic, gamma‐aminobutyric acid (GABAergic), and probably glycinergic neurons . These different neuron types are not distributed uniformly within the PPN.…”

“…Although the original conception of the role of cholinergic PPN neurons focused on the regulation of brain stem control of locomotion, these neurons have a major rostral projection to the thalamus, suggesting a role in modulation of sensory information . This concept is supported by research in PD patients indicating a role for these projections in sensory integration to maintain normal posture and detection of salient external cues …”