The mesopontine tegmentum in reward and aversion: From cellular heterogeneity to behaviour

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 162, P. 105702 - 105702

Published: May 6, 2024

The mesopontine tegmentum, comprising the pedunculopontine tegmentum (PPN) and laterodorsal (LDT), is intricately connected to various regions of basal ganglia, motor systems, limbic systems. PPN LDT can regulate activity different brain these target in this way are a privileged position modulate motivated behaviours. Despite recent findings, have been largely overlooked discussions about neural circuits associated with reward aversion. This review aims provide timely comprehensive resource on past current research, highlighting LDT's connectivity influence ganglia limbic, Seminal studies, including lesion, pharmacological, optogenetic/chemogenetic approaches, demonstrate their critical roles modulating reward/aversive emphasizes need for further investigation into cellular mechanisms, order clarify role behaviour contribution neuropsychiatric disorders.

Language: Английский

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Upper brainstem cholinergic neurons project to ascending and descending circuits

BMC Biology, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 6, 2023

Abstract Background Based on their anatomical location, rostral projections of nuclei are classified as ascending circuits, while caudal descending circuits. Upper brainstem neurons participate in complex information processing and specific sub-populations preferentially project to participating or Cholinergic the upper have extensive collateralizations both circuits; however, single-cell projection patterns remain unclear because lack comprehensive characterization individual neurons. Results By combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired a high-resolution whole-brain dataset pontine-tegmental cholinergic (PTCNs) reconstructed detailed morphology using semi-automatic reconstruction methods. As main source acetylcholine some subcortical areas, PTCNs had abundant axons lengths up 60 cm 5000 terminals innervated multiple brain regions from spinal cord cortex hemispheres. various collaterals were grouped into four subtypes. The pedunculopontine nucleus was more divergent, whereas laterodorsal tegmental contained richer axonal branches dendrites. In thalamus three different projected via two separate pathways. Moreover, targeting ventral area substantia nigra pontine reticular nuclei, these circuits contributed oppositely locomotion. Conclusions Our results suggest that axons, most simultaneously. They target patterns, such cortex. These provide organizational understand connexional logic brainstem.

Language: Английский

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Multimodal gradients of basal forebrain connectivity across the neocortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 26, 2023

The cholinergic innervation of the cortex originates almost entirely from populations neurons in basal forebrain (BF). Structurally, ascending BF projections are highly branched, with individual cells targeting multiple different cortical regions. However, it is not known whether structural organization reflects their functional integration cortex. We therefore used high-resolution 7T diffusion and resting state MRI humans to examine multimodal gradients connectivity Moving anteromedial posterolateral BF, we observed reduced tethering between gradients, most pronounced dissimilarity localized nucleus basalis Meynert (NbM). expression this structure-function gradient revealed progressively weaker moving unimodal transmodal cortex, lowest midcingulo-insular human [ 18 F] fluoroethoxy-benzovesamicol (FEOBV) PET demonstrate that areas higher concentrations tend exhibit lower connectivity, suggesting a pattern increasingly diffuse axonal arborization. Anterograde viral tracing FEOBV mice confirmed arborization across neurons. Like humans, highest project cingulo-insular mouse isocortex. Altogether, our findings reveal vary branch complexity, certain subpopulations exhibiting greater modularity others diffusivity targets.

Language: Английский

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The regulation of the pedunculopontine tegmental nucleus in sleep–wake states

Sleep and Biological Rhythms, Journal Year: 2023, Volume and Issue: 22(1), P. 5 - 11

Published: Sept. 26, 2023

Abstract The pedunculopontine tegmental nucleus (PPTg) plays a vital role in sleep/wake states. There are three main kinds of heterogeneous neurons involved: cholinergic, glutamatergic, and gamma-aminobutyric acidergic (GABAergic) neurons. However, the precise roles glutamatergic GABAergic PPTg cell groups regulating sleep–wake unknown. Recent work suggests that may activate arousal-promoting nucleus, thus exerting their wakefulness effects. We review related projection pathways functions various PPTg, especially mechanisms sleep–wake, providing new perspectives for research mechanisms.

Language: Английский

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Subregion and sex differences in ethanol activation of cholinergic and glutamatergic cells in the mesopontine tegmentum

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 2, 2024

Abstract Ethanol engages cholinergic signaling and elicits endogenous acetylcholine release. Acetylcholine input to the midbrain originates from mesopontine tegmentum (MPT), which is composed of laterodorsal (LDT) pedunculopontine tegmental nucleus (PPN). We investigated effect acute chronic ethanol administration on glutamatergic neuron activation in PPN LDT male female mice. show that activates neurons not Chronic 15 daily injections 2 g/kg induced Fos expression mice, whereas did increase neuronal LDT. A single 4 injection, but a In contrast, or at either dose duration had no MPT Female mice higher baseline level compared with males. also found population co-labeled were highly active saline- ethanol-treated groups both sexes. These findings illustrate complex differential effects across dose, time point, subregion sex.

Language: Английский

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Activation of Pedunculopontine Tegmental Nucleus Alleviates the Pain Induced by the Lesion of Midbrain Dopaminergic Neurons

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5636 - 5636

Published: May 22, 2024

The loss of midbrain dopaminergic (DA) neurons is the fundamental pathological feature Parkinson’s disease (PD). PD causes chronic pain in two-thirds patients. Recent studies showed that activation pedunculopontine tegmental nucleus (PPTg) can effectively relieve inflammatory and neuropathic pain. PPTg located pontomesencephalic tegmentum, a target deep brain stimulation (DBS) treatment PD, involved motor control sensory integration. To test whether lesion DA induced hypersensitivity, chemogenetic could modulate pain, AAV-hM3Dq receptor was transfected expressed into 6-hydroxydopamine-lesioned mice. In this study, von Frey, open field, adhesive tape removal tests were used to assess animals’ sensitivity, locomotor activity, sensorimotor function somatosensory perception, respectively. Here, we found minor deficit voluntary movement but did not affect perception test. results led which be alleviated both by levodopa PPTg. Activating may potential therapeutic strategy phenotypes PD.

Language: Английский

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A review of cell-type specific circuit mechanisms underlying epilepsy

Acta Epileptologica, Journal Year: 2024, Volume and Issue: 6(1)

Published: June 1, 2024

Abstract Epilepsy is a prevalent neurological disorder, yet its underlying mechanisms remain incompletely understood. Accumulated studies have indicated that epilepsy characterized by abnormal neural circuits. Understanding the circuit crucial for comprehending pathogenesis of epilepsy. With advances in tracing and modulating tools circuits, some epileptic circuits been uncovered. This comprehensive review focuses on various neuronal subtypes, elucidating their distinct roles. Epileptic seizures are primarily hyperactivity glutamatergic neurons inhibition GABAergic neurons. However, specific activated suppressed exacerbate through preferentially regulating activity within Distinct subtypes contribute differently to activities, potentially due diverse connection patterns. Moreover, identical may assume roles different stages Both with long-range projecting fibers innervate multiple nuclei; nevertheless, not all these activities. originating from same nuclei display contributions certain even exert opposing effects Neuromodulatory neurons, including cholinergic, serotonergic, dopaminergic, noradrenergic also implicated epilepsy, although poorly These suggest establish intricate connections cell-type-specific play pivotal there still limitations knowledge methods, further understanding crucial, particularly context refractory

Language: Английский

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L-type calcium channel blockade with verapamil prevents noise induced neuronal dyssynchrony

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Abstract Previous studies have established the protective effects of calcium channel blockade on peripheral auditory system in response to noise exposure. While these implicate L-type channels (LTCCs) generated dysfunction periphery, contributions LTCCs noise-induced central remains unclear. To begin elucidate roles hearing, and function were assessed longitudinally after LTCC blockade. Neuronal synchrony activity by analyzing wave I (peripheral) V (central) brainstem responses (ABRs). Just prior a exposure resulting temporary shift hearing thresholds, rats administered verapamil (LTCC blocker) or saline. Verapamil administration prevented decrease ABR amplitudes. Interestingly, when non-noise exposed animals verapamil, amplitude decreased, suggesting that are critical for neuronal inferior colliculus. The colliculus mediates inhibition acoustic startle reflex (giASR). Following giASR was enhanced, but enhancement not These results suggest while necessary auditory-related synchronous activity, do contribute hyperactivity

Language: Английский

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Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and globus pallidus externa (GPe) will have specific effects on locomotion: SNr inhibiting locomotion GPe enhancing it. In this manuscript, we use in vivo optogenetics to show a projection-defined neural subpopulation within each structure exerts non-canonical locomotion. These subpopulations are defined by their projection pedunculopontine nucleus (PPN) mediate opposing reward. To understand how these structures differentially modulate PPN, ex whole-cell recording with comprehensively dissect connections regionally- molecularly-defined populations of PPN neurons. inhibits all subtypes, but most strongly caudal glutamatergic selectively GABAergic neurons, avoiding both cholinergic rostral cells. This circuit characterization reveals pathways for valence.

Language: Английский

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Multimodal gradients of basal forebrain connectivity across the neocortex

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 18, 2024

Cortical cholinergic projections originate from subregions of the basal forebrain (BF). To examine its organization in humans, we computed multimodal gradients BF connectivity by combining 7 T diffusion and resting state functional MRI. Moving anteromedial to posterolateral BF, observe reduced tethering between structural gradients, with lowest nucleus basalis Meynert. In neocortex, this gradient is expressed progressively unimodal sensory transmodal cortex, midcingulo-insular network, also spatially correlated molecular concentration VAChT, measured [

Language: Английский

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