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

Peppe, Antonella; Galati, Salvatore; Bassi, Mario Stampanoni; D′Angelo, Vincenza; Pierantozzi, Mariangela

doi:10.3389/fneur.2013.00068

Cited by 35 publications

(33 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, however, numerous studies have described that patients often feel subjectively more “alert” upon the onset of low frequency (15-25Hz) DBS in the PPN (Stefani et al, 2013). Our data can provide a potential explanation for these findings, demonstrating that the MLR/PPN mediates both locomotion as well as changes in behavioral state that are naturally recruited in tandem.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion

Lee

Hoy

Bonci

et al. 2014

Neuron

279

254

View full text Add to dashboard Cite

Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate the intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and shifts in cortical processing. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain could also enhance cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion

Lee

Hoy

Bonci

et al. 2014

Neuron

279

254

View full text Add to dashboard Cite

show abstract

“…When stimulated, patients commonly report a heightened feeling of alertness (Stefani et al 2013). It is plausible that alertness would be the subjective feeling associated with the high-gate state of cortex; however, we do not know whether locomotion induces a high-gain state in human visual cortex.…”

Section: Discussionmentioning

confidence: 99%

A Neural Circuit That Controls Cortical State, Plasticity, and the Gain of Sensory Responses in Mouse

Stryker

2014

Cold Spring Harb Symp Quant Biol

View full text Add to dashboard Cite

Neurons in the visual cortex were first found to be exquisitely selective for particular properties of visual stimuli in anesthetized animals, including mice. Studies of alert mice in an apparatus that allowed them to stand or run revealed that locomotion causes a change in cortical state that dramatically increases the magnitude of responses in neurons of the visual cortex without altering selectivity, effectively changing the gain of sensory responses. Locomotion also dramatically enhances adult plasticity in the recovery from long-term visual deprivation. We have studied the elements and operation of the neural circuit responsible for the enhancement of activity and shown that it enhances plasticity even in mice not free to run. The circuit consists of projections ascending from the midbrain locomotor region (MLR) to the basal forebrain, activating cholinergic and perhaps other projections to excite inhibitory interneurons expressing vasoactive intestinal peptide (VIP) in the visual cortex. VIP cells activated by locomotion inhibit interneurons that express somatostatin (SST), thereby disinhibiting the excitatory principal neurons and allowing them to respond more strongly to effective visual stimuli. These findings reveal in alert animals how the ascending reticular activating system described in anesthetized animals 50 years ago operates to control cortical state.

show abstract

“…Moro et al (2010) used unilateral stimulation at 50 Hz and 70 Hz, and showed improvements in falls and motor scores. Stefani et al (2007, 2013) used PPN stimulation at 10 Hz and 25 Hz, with some improvements in motor scores but a significant improvement in sleep patterns and modest improvement in gait. Alessandro et al (2010) using 25 Hz stimulation showed no motor improvements but significant amelioration in sleep scores and executive function.…”

Section: Implications For Dbsmentioning

confidence: 99%

“…Studies need to be performed to determine the effects of short- and long-term PPN DBS on cortical high frequency EEG activity. There is some information that PPN DBS may improve cognitive function (Tyckoki et al 2011), and that low frequency stimulation (5–30 Hz) may improve executive and higher functions (Stefani et al 2013), but this issue needs further elucidation. After all, lesions of the PPN disturb attention, executive function and working memory (Winn 2008).…”

Section: Suggestions For the Futurementioning

confidence: 99%

The physiology of the pedunculopontine nucleus: implications for deep brain stimulation

et al. 2014

View full text Add to dashboard Cite

This brief review resolves a number of persistent conflicts regarding the location and characteristics of the mesencephalic locomotor region (MLR), which has in the past been described as not locomotion-specific and is more likely the pedunculopontine nucleus (PPN). The parameters of stimulation used to elicit changes in posture and locomotion we now know are ideally suited to match the intrinsic membrane properties of PPN neurons. The physiology of these cells is important not only because it is a major element of the reticular activating system (RAS), but also because it is a novel target for the treatment of gait and postural deficits in Parkinson’s disease (PD). The discussion explains many of the effects reported following deep brain stimulation (DBS) of the PPN by different groups, and provides guidelines for the determination of long-term assessment and effects of PPN DBS. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from DBS for movement disorders. Despite these improvements, there remains a great opportunity for further understanding of the mechanisms through which DBS has its effects and for further development of appropriate technology to effect these treatments. We review the scientific basis for one of the newest targets, the PPN, in the treatment of PD and other movement disorders, and address the needs for further investigation.

show abstract

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

Cited by 35 publications

References 109 publications

Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion

Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion

A Neural Circuit That Controls Cortical State, Plasticity, and the Gain of Sensory Responses in Mouse

The physiology of the pedunculopontine nucleus: implications for deep brain stimulation

Contact Info

Product

Resources

About