Cholinergic input from the pedunculopontine nucleus to the cerebellum: implications for deep brain stimulation in Parkinson's disease

Deep brain stimulation（DBS）is a well established electrophysiological treatment initially applied to treat medication-refractory motor symptoms in Parkinson＇s disease（PD）,and is now being explored for several neurological and psychiatric disorders.The specific physiological mechanisms underlying the effectiveness of DBS are not fully understood.

Unusual neural tract between injured fornix and pedunculopontine nucleus in a patient with traumatic brain injury

It has been known that four cholinergic nuclei are located in the septal region and basal forebrain （Ch 1： medial septal nucleus, Ch 2： vertical nucleus of the diagonal band, Ch 3： horizontal limb of the diagonal band and Ch 4： nucleus basalis of Meynert） and two are located in the brainstem （Ch 5： pedunculopontine nucleus and Ch 6： laterodorsal tegmental nucleus） （Selden et al., 1998; Lucas-Meunier et al., 2003; Mesulam, 2004; Nieuwenhuys et al., 2007）. The fornix transfers information on episodic mem- ory between the medial diencephalon and the medial temporal lobe （Afifi and Bergman, 2005; Wolk and Budson, 2010）. The fornix is known to obtain cholinergic innervation from Ch 1 and Ch 2, and to project to the hippocampal formation （Selden et al., 1998; Lucas-Meunier et al., 2003; Mesulam, 2004; Nieu- wenhuys et al., 2007; Dere et al., 2008; Naidich and Duvernoy, 2009; Isaacson and Pribram, 2013）.

Dynamic analysis of beta oscillations in Parkinsonian neural networks with the pedunculopontine nucleus under optogenetic control

Clinical experiments have proven that the pedunculopontine nucleus(PPN)plays a crucial role in the modulation of beta oscillations in Parkinson’s disease(PD).Here,we propose a new computational framework by introducing the PPN and related synaptic connections to the classic basal ganglia-thalamo-cortical model.Fascinatingly,the improved model can not only simulate the basic saturated and beta activities mentioned in previous studies but also produce the normal alpha rhythm that is much closer to physiological phenomena.Specifically,the results show that Parkinsonian oscillation activities can be controlled and modulated by the connection strength between the PPN and the globus pallidus internal nucleus(GPi)and the subthalamic nucleus(STN),supporting the fact that PPN is overinhibited in PD.Meanwhile,the internal mechanism underlying these state transitions is further explained from the perspective of dynamics.Additionally,both deep brain stimulation(DBS)and optogenetic technology are considered effective in terms of abnormal oscillations.Especially when a low-frequency DBS is added to the PPN,beta oscillations can be suppressed,but it is excited again as the DBS’s frequency gradually increases to a larger value.These results coincide with the experimental results that low-frequency stimulation of the PPN is effective,and verify the rationality of the model.Furthermore,we show that optogenetic stimulation of the globus pallidus external(GPe)expressing excitatory channelrhodopsin(ChR2)can effectively inhibit beta oscillations,whereas exciting the STN and PPN has a limited effect.These results are consistent with experimental reports suggesting that the symptoms of PD’s movement disorder can be alleviated under the GPe-ChR2,but not STN-ChR2,situation.Although the functional role of the PPN and the feasibility of optogenetic stimulation remain to be clinically explored,the results obtained help us understand the mechanisms of beta oscillations in PD.

Laterodorsal Tegmentum and Pedunculopontine Tegmental Nucleus Circuits Regulate Renal Functions: Neuroanatomical Evidence in Mice Models

Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.