1. Rethinking the Pedunculopontine Nucleus: From Cellular Organization to Function 
Juan Mena-Segovia, J. Paul Bolam 
Neuron 
Volume 94, Issue 1, Pages 7-18 (April 2017)
DOI: /j.neuron
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2. Figure 1 Connectivity of PPN Cholinergic Neurons
(A) Single-cell tracing studies have revealed a high-degree collateralization of the axons of cholinergic neurons, showing that individual neurons innervate most of the known targets of cholinergic neurons (only one neuron is illustrated). Shaded area represents the PPN outline.
(B) Three main axonal trajectories define cholinergic neurons: an ascending dorsal stream, an ascending ventral stream, and a descending projection. The striatal projection may originate from the dorsal stream. Darker boxes indicate those regions in which synaptic contacts of PPN cholinergic neurons have been identified, and the lighter boxes indicate those regions in which PPN cholinergic axons have been observed but without confirmation of synaptic contacts.
Abbreviations: Ant, anterior thalamus; CL, centrolateral thalamic nucleus; GiN, gigantocellular nucleus; IC, inferior colliculus; PF, parafascicular nucleus; PnO, nucleus pontis oralis; PnC, nucleus pontis caudalis; Rt, reticular thalamic nucleus; SC, superior colliculus; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; STN, subthalamic nucleus; VTA, ventral tegmental area. Data in (A) are reproduced from Mena-Segovia et al. (2008).
Neuron  , 7-18DOI: ( /j.neuron )
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3. Figure 2 Topographical Organization of the Cholinergic Brainstem
Cholinergic neurons of the PPN and LDT innervate a similar array of forebrain targets but maintain a clear topographical organization. Neurons of the rostral PPN (PPNr) preferentially innervate motor-related circuits such as the SNc, the dorsolateral striatum (DLS), and the intralaminar thalamus. In contrast, neurons of the LDT preferentially innervate limbic-related circuits such as the VTA, the dorsomedial striatum (DMS), and the midline thalamus. The caudal PPN (PPNc) provides innervation to both motor and limbic structures as well as other associative regions. Abbreviations: IL, intralaminar thalamic nuclei; Mid, midline thalamic nuclei; SNc, substantia nigra pars compacta; VTA, ventral tegmental area.
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4. Figure 3 Local Connectivity in the PPN
(A and A’) In (A), a reconstructed single-PPN non-cholinergic neuron is represented whose axon is contained within the boundaries of the PPN (A’), suggesting the existence of interneurons. Blue dots represent axonal varicosities. Reconstruction by H. Ros; scp, superior cerebellar peduncle.
(B) Detail of the PPN cholinergic neuron depicted in Figure 1 showing a large number of local axonal varicosities in the proximity of the cell body and dendrites.
(C) Local asymmetric synapse (arrow) arising from the same cholinergic neuron (b, bouton; d, dendrite).
(D) Local asymmetric synapses arising from a non-cholinergic PPN neuron in contact with two dendritic processes.
(E) Cholinergic neurons (ChAT-positive) give rise to a larger number of local axonal varicosities than non-cholinergic neurons (mean ± SEM).
Data in (B), (C), and (E) are reproduced from Mena-Segovia et al. (2008), and data in (D) are reproduced from Ros et al. (2010).
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5. Figure 4 Discharge Properties of Cholinergic Neurons
(A) High-density in vivo electrophysiological recordings during brain state transitions that were elicited by sensory stimulation (STIM) in rats under urethane anesthesia. PPN neurons display a range of dynamics, including phasic, tonic, and inhibitory responses.
(B) Identified cholinergic neurons juxtacellularly recorded and labeled show transient patterns of activation during sensory stimulation and transitions to a global activated state. ECoG, electrocorticogram.
(C) Neurons with phasic responses during brain state transitions were identified as cholinergic (Ch+), whereas neurons with tonic or inhibitory (inhib.) responses were identified as non-cholinergic (NCh).
(D) Intrinsic properties of cholinergic neurons revealed in an ex vivo preparation. Train of action potentials elicited by current injection showed a high adaptation index (top, single trace; bottom, group data). freq., frequency.
(E) Comparable adaptation dynamics in vivo and in vitro, as shown by the decay of the instantaneous firing rate modeled by an exponential function with adaptation exponent (τ) (boxes represent median, quartiles 25/75 and percentiles 5/95).
Data are reproduced from Petzold et al. (2015).
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6. Figure 5 Functional Connectivity Map of Cholinergic Neurons
Ascending projections from cholinergic neurons converge directly and indirectly at the level of the striatum. Activation of the mesostriatal system has been associated with reinforcement of actions, whereas activation of the thalamostriatal system likely processes salient stimuli and influences the behavioral state. A consequence of thalamic activation is the generation of thalamic and cortical gamma oscillations, usually associated with attentional and motivational states. Activation of the colliculi contributes to the modulation of attentional shifts and saccadic movement, whereas the activation of the STN will directly interfere with the basal ganglia output. Descending projections from cholinergic neurons have been shown to inhibit movement and muscle tone. Thus, the activation of cholinergic neurons may trigger a behavioral response aimed to inhibit previous actions and facilitate new associations while enhancing the processing of salient events. Abbreviations: Ant, anterior thalamus; GiN, gigantocellular nucleus; IC, inferior colliculus; PF, parafascicular nucleus; PnO, nucleus pontis oralis; PnC, nucleus pontis caudalis; Rt, reticular thalamic nucleus; SC, superior colliculus; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; STN, subthalamic nucleus; VTA, ventral tegmental area.
Neuron  , 7-18DOI: ( /j.neuron )
Copyright © 2017 Elsevier Inc. Terms and Conditions