Critical evaluation of the anatomical location of the Barrington nucleus: Relevance for deep brain stimulation surgery of pedunculopontine tegmental nucleus

Blanco, Lisette; Yuste, José; Sauvage, María Angeles Carrillo-de; Gómez, Abraham Bernárdez; Fernández-Villalba, Emiliano; Avilés-Olmos, Itciar; Limousin, Patricia; Zrinzo, Ludvic; Herrero, M.T.

doi:10.1016/j.neuroscience.2013.05.047

Cited by 16 publications

(10 citation statements)

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“…Thus far, even after colchicine treatment we have not had good results immunolabeling CRH in mice. To our knowledge, two previous groups have claimed to label Bar CRH neurons in mice after colchicine treatment; one did not show any images (Wang et al, ), and the other presenting an image with immunoreactivity in punctae, not cell bodies (Blanco et al, ). Even if we were to identify an antiserum or tissue protocol to immunolabel CRH in mice, preinjecting a neurotoxin is impractical for routine histologic assays and would not allow us to identify living Bar CRH neurons for in vivo calcium imaging or slice electrophysiology.…”

Section: Discussionmentioning

confidence: 81%

“…In cats, Holstege and colleagues identified a homologous spinally projecting population, rostral and ventromedial to the LC (Holstege et al, ), which they named the “M‐region.” Yet even in this species—the primary source of micturition physiology beginning with Barrington in the early 20th century (Barrington, ; Kabat, Magoun, & Ranson, ; Tang, )—we lack basic information about gene and protein markers, including CRH. In humans, nonhuman primates, and other species we know even less (Blanco et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Yet even in this species-the primary source of micturition physiology beginning with Barrington in the early 20th century (Barrington, 1927;Kabat, Magoun, & Ranson, 1936;Tang, 1955)-we lack basic information about gene and protein markers, including CRH. In humans, nonhuman primates, and other species we know even less (Blanco et al, 2013).…”

Section: Basic Nomenclaturementioning

confidence: 99%

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Barrington's nucleus: Neuroanatomic landscape of the mouse “pontine micturition center”

Verstegen

VanderHorst

Gray

et al. 2017

J of Comparative Neurology

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Barrington’s nucleus (Bar) is thought to contain neurons that trigger voiding and thereby function as the “pontine micturition center.” Lacking detailed information on this region in mice, we examined gene and protein markers to characterize Bar and the neurons surrounding it. Like rats and cats, mice have an ovoid core of medium-sized Bar neurons located medial to the locus coeruleus (LC). Bar neurons express a GFP reporter for Vglut2, develop from a Math1/Atoh1 lineage, and exhibit immunoreactivity for NeuN. Many neurons in and around this core cluster express a reporter for corticotrophin-releasing hormone (BarCRH). Axons from BarCRH neurons project to the lumbosacral spinal cord and ramify extensively in two regions: the dorsal gray commissural and intermediolateral nuclei. BarCRH neurons have unexpectedly long dendrites, which may receive synaptic input from the cerebral cortex and other brain regions beyond the core afferents identified previously. Finally, at least five populations of neurons surround Bar: rostral-dorsomedial cholinergic neurons in the laterodorsal tegmental nucleus; lateral noradrenergic neurons in the LC; medial GABAergic neurons in the pontine central gray; ventromedial, small GABAergic neurons that express FoxP2; and dorsolateral glutamatergic neurons that express FoxP2 in the pLC and form a wedge dividing Bar from the dorsal LC. We discuss the implications of this new information for interpreting existing data and future experiments targeting BarCRH neurons and their synaptic afferents to study micturition and other pelvic functions.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Basic Nomenclaturementioning

confidence: 99%

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Barrington's nucleus: Neuroanatomic landscape of the mouse “pontine micturition center”

Verstegen

VanderHorst

Gray

et al. 2017

J of Comparative Neurology

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“…These YFP-positive neurons were clustered as a small and roughly sphere-shape region of ~300μm in diameter seen in only one 300μm brain slice or split in two adjacent slices. This group of cells was located immediately below the 4 th ventricle dorsomedial to the LC and just dorsal to Barrington’s nucleus ( Fig 1C and 1E ) [ 12 ]. Some of the YFP-positive cells overlapped with DBH-positive neurons in the LC, although no cells with double labeling of both DBH ( Fig 1F ) and YFP were found ( Fig 1G ).…”

Section: Resultsmentioning

confidence: 99%

Identification of a Group of GABAergic Neurons in the Dorsomedial Area of the Locus Coeruleus

Jin

Bondy

et al. 2016

PLoS ONE

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The locus coeruleus (LC)-norepinephrine (NE) system in the brainstem plays a critical role in a variety of behaviors is an important target of pharmacological intervention to several neurological disorders. Although GABA is the major inhibitory neurotransmitter of LC neurons, the modulation of LC neuronal firing activity by local GABAergic interneurons remains poorly understood with respect to their precise location, intrinsic membrane properties and synaptic modulation. Here, we took an optogenetic approach to address these questions. Channelrhodopsin (ChR2) in a tandem with the yellow fluorescent protein (YFP) was expressed in GABAergic neurons under the control of glutamic acid decarboxylase 2 (GAD2) promoter. Immediately dorsomedial to the LC nucleus, a group of GABAergic neurons was observed. They had small soma and were densely packed in a small area, which we named the dorsomedial LC or dmLC nucleus. These GABAergic neurons showed fast firing activity, strong inward rectification and spike frequency adaptation. Lateral inhibition among these GABAergic neurons was observed. Optostimulation of the dmLC area drastically inhibited LC neuronal firing frequency, expanded the spike intervals, and reset their pacemaking activity. Analysis of the light evoked inhibitory postsynaptic currents (IPSCs) indicated that they were monosynaptic. Such light evoked IPSCs were not seen in slices where this group of GABAergic neurons was absent. Thus, an isolated group of GABAergic neurons is demonstrated in the LC area, whose location, somatic morphology and intrinsic membrane properties are clearly distinguishable from adjacent LC neurons. They interact with each and may inhibit LC neurons as well as a part of local neuronal circuitry in the LC.

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“…The nucleus ventralis intermedius (VIM) of the thalamus is a standard target for alleviating tremor in PD. 125 The pedunculopontine tegmental nucleus is a target for gait disorder 25,171 and sleep modulation, 159 sometimes in tandem with stimulation of other nuclei. 90,195 Other targets in early stages of exploration include the posterior subthalamic area, caudal zona incerta, prelemniscal radiation, thalamic centromedian-parafascicular complex, and cerebral cortex.…”

Section: Current Approach To Therapymentioning

confidence: 99%

Deep brain stimulation: a mechanistic and clinical update

Karas

Mikell

Christian

et al. 2013

FOC

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Deep brain stimulation (DBS), the practice of placing electrodes deep into the brain to stimulate subcortical structures with electrical current, has been increasing as a neurosurgical procedure over the past 15 years. Originally a treatment for essential tremor, DBS is now used and under investigation across a wide spectrum of neurological and psychiatric disorders. In addition to applying electrical stimulation for clinical symptomatic relief, the electrodes implanted can also be used to record local electrical activity in the brain, making DBS a useful research tool. Human single-neuron recordings and local field potentials are now often recorded intraoperatively as electrodes are implanted. Thus, the increasing scope of DBS clinical applications is being matched by an increase in investigational use, leading to a rapidly evolving understanding of cortical and subcortical neurocircuitry. In this review, the authors discuss recent innovations in the clinical use of DBS, both in approved indications as well as in indications under investigation. Deep brain stimulation as an investigational tool is also reviewed, paying special attention to evolving models of basal ganglia and cortical function in health and disease. Finally, the authors look to the future across several indications, highlighting gaps in knowledge and possible future directions of DBS treatment.

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Critical evaluation of the anatomical location of the Barrington nucleus: Relevance for deep brain stimulation surgery of pedunculopontine tegmental nucleus

Cited by 16 publications

References 56 publications

Barrington's nucleus: Neuroanatomic landscape of the mouse “pontine micturition center”

Barrington's nucleus: Neuroanatomic landscape of the mouse “pontine micturition center”

Identification of a Group of GABAergic Neurons in the Dorsomedial Area of the Locus Coeruleus

Deep brain stimulation: a mechanistic and clinical update

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