Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: Time- and site-specific effects on two-way active avoidance conditioning

Andero, Raül; Torras-Garcia, Meritxell; Quiroz‐Padilla, María Fernanda; David, Cristhian; Coll-Andreu, Margalida

doi:10.1016/j.nlm.2006.11.002

Cited by 7 publications

(5 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Electrical stimulation of the PPT has been demonstrated to increase cortical arousal (Dringenberg and Olmstead, 2003), enhance cortical acetylcholine release (Rasmusson et al, 1994) and facilitate conditioned learning (Andero et al, 2007). The current finding that the combination treatment activates the PPT, supports our previous observations that idalopirdine potentiates the effects of donepezil on cortical extracellular ACh levels and excitability, manifested as gamma oscillations in the EEG (Amat-Foraster et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The Serotonin Receptor 6 Antagonist Idalopirdine and Acetylcholinesterase Inhibitor Donepezil Have Synergistic Effects on Brain Activity—A Functional MRI Study in the Awake Rat

et al. 2017

View full text Add to dashboard Cite

The 5-HT6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD) and other CNS disorders. The high-affinity and selective 5-HT6 receptor antagonist idalopirdine (Lu AE58054) is currently in development for mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of idalopirdine alone and in combination with the AChEI donepezil on brain activity using BOLD (Blood Oxygen Level Dependent) functional magnetic resonance imaging (fMRI) in the awake rat. Idalopirdine (2 mg/kg, i.v.) alone had a modest effect on brain activity, resulting in activation of eight brain regions at the peak response. Of these, the cholinergic diagonal band of Broca, the infralimbic cortex, the ventral pallidum, the nucleus accumbens shell, and the magnocellular preoptic area were shared with the effects of donepezil (0.3 mg/kg, i.v.). Donepezil alone activated 19 brain regions at the peak response, including several cortical regions, areas of the septo-hippocampal system and the serotonergic raphe nucleus. When idalopirdine and donepezil were combined, there was a robust stimulation pattern with activation of 36 brain regions spread across the extended-amygdala-, striato-pallidal, and septo-hippocampal networks as well as the cholinergic system. These findings indicate that, whilst idalopirdine and donepezil recruit a number of overlapping regions including one of the forebrain cholinergic nuclei, the synergistic effect of both compounds extends beyond the cholinergic system and the effects of donepezil alone toward recruitment of multiple neural circuits and neurotransmitter systems. These data provide new insight into the mechanisms via which idalopirdine might improve cognition in donepezil-treated AD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

The Serotonin Receptor 6 Antagonist Idalopirdine and Acetylcholinesterase Inhibitor Donepezil Have Synergistic Effects on Brain Activity—A Functional MRI Study in the Awake Rat

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Behavioral studies following restricted lesions or selective manipulations in the rostral and caudal PPN have shown functional differences between these two PPN areas that correlate with the functional domains defined by the neurochemical distribution and connectivity (Inglis et al, 2001; Alderson et al, 2006, 2008; Andero et al, 2007). Such functional differences have relevance for deep brain stimulation (DBS) therapy in the PPN in Parkinson's disease patients (Starr et al, 1998; Pahapill and Lozano, 2000; Nandi et al, 2002; Benabid, 2003; Jenkinson et al, 2005; Stefani et al, 2007).…”

Section: Functional Implications Of Topographymentioning

confidence: 99%

Topographical Organization of the Pedunculopontine Nucleus

Bolam²,

2011

View full text Add to dashboard Cite

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.

show abstract

“…As known, PPN-a, part of the reticular activating system, plays a critical role in regulating the sleep-awake cycle and facilitating arousal mechanisms (Steriade et al, 1990a; Rye, 1997; Datta, 2002). PPN-a is also strongly involved in other facets of behavior including motivation, attention, reward, and mnemonic processes (Steckler et al, 1994; Winn, 2006; Andero et al, 2007; Ros et al, 2010). …”

Section: State-of-the-art Of Motor and Non-motor Effects Of Ppn-dbsmentioning

confidence: 99%

The Serendipity Case of the Pedunculopontine Nucleus Low-Frequency Brain Stimulation: Chasing a Gait Response, Finding Sleep, and Cognition Improvement

Peppe¹,

Galati²,

Bassi³

et al. 2013

Front. Neurol.

View full text Add to dashboard Cite

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficacious therapy for Parkinson’s disease (PD) but its effects on non-motor facets may be detrimental. The low-frequency stimulation (LFS) of the pedunculopontine nucleus (PPN or the nucleus tegmenti pedunculopontini – PPTg-) opened new perspectives. In our hands, PPTg-LFS revealed a modest influence on gait but increased sleep quality and degree of attentiveness. At odds with potential adverse events following STN-DBS, executive functions, under PPTg-ON, ameliorated. A recent study comparing both targets found that only PPTg-LFS improved night-time sleep and daytime sleepiness. Chances are that different neurosurgical groups influence either the PPN sub-portion identified as pars dissipata (more interconnected with GPi/STN) or the caudal PPN region known as pars compacta, preferentially targeting intralaminar and associative nucleus of the thalamus. Yet, the wide electrical field delivered affects a plethora of en passant circuits, and a fine distinction on the specific pathways involved is elusive. This review explores our angle of vision, by which PPTg-LFS activates cholinergic and glutamatergic ascending fibers, influencing non-motor behaviors.

show abstract

Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: Time- and site-specific effects on two-way active avoidance conditioning

Cited by 7 publications

References 45 publications

The Serotonin Receptor 6 Antagonist Idalopirdine and Acetylcholinesterase Inhibitor Donepezil Have Synergistic Effects on Brain Activity—A Functional MRI Study in the Awake Rat

The Serotonin Receptor 6 Antagonist Idalopirdine and Acetylcholinesterase Inhibitor Donepezil Have Synergistic Effects on Brain Activity—A Functional MRI Study in the Awake Rat

Topographical Organization of the Pedunculopontine Nucleus

The Serendipity Case of the Pedunculopontine Nucleus Low-Frequency Brain Stimulation: Chasing a Gait Response, Finding Sleep, and Cognition Improvement

Contact Info

Product

Resources

About