Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus

Baksa, Brigitta; Kovács, Attila; Bayasgalan, Tsogbadrakh; Szentesi, Péter; Kőszeghy, Áron; Szûcs, Péter; Pál, Balázs

doi:10.1007/s00018-019-03025-4

Cited by 13 publications

(12 citation statements)

References 70 publications

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“…We found that different projection patterns of PTCNs in the PPN and LDT had rich dendrites ( Figure 3B ). Consistent with previous studies (Baksa et al, 2019), we divided the dendrites with bipolar and multipolar dendritic trees according to the distribution of longer dendrites ( Figure 3B ) and found a few of them had bipolar dendritic trees while most were multipolar (Figure 3—figure supplement 1). Then we analyzed the spatial distribution of dendritic branches with the Sholl analysis ( Figure 3C ).…”

Section: Resultssupporting

confidence: 86%

Simultaneously cholinergic projection in Ascending and Descending Circuits from Midbrain

Zhao

Jiang

Wang

et al. 2022

Preprint

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The midbrain participates in complex neural information processing in the ascending and descending circuits, but their organization remains unclear due to the lack of comprehensive dissection of the characterization of individual neurons. Combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired the whole-brain dataset with high resolution and reconstructed the detailed morphology of the pontine-tegmental cholinergic neurons (PTCNs). As the main cholinergic system of the midbrain, the individual PTCNs own abundant axons with length up to 60 cm and 5000 terminal branches and innervate multiple brain regions from the spinal cord to cortex in both hemispheres. According to various targeting regions in the ascending and descending circuits, individual PTCNs could be grouped into four types and the axonal fibers of cholinergic neurons in the pedunculopontine nucleus present more divergent while neurons in the laterodorsal tegmental nucleus contain richer axonal fibers and dendrites. In the axonal targeting nuclei, such as in the thalamus or cortex, the individual neurons innervate multiple sub-regions with separate pathways. These results provide the detailed organization characterization of the cholinergic neurons to understand the connection logic of the midbrain.

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Section: Resultssupporting

confidence: 86%

Simultaneously cholinergic projection in Ascending and Descending Circuits from Midbrain

Zhao

Jiang

Wang

et al. 2022

Preprint

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“…We observed that KCNQ4-possessing cholinergic neurons are rather located in the caudal PPN. This observation strengthens the view that PPN neurons are far from uniform, but have several functional subgroups in terms of membrane properties ( Baksa et al, 2019 ). Furthermore, the rostral PPN (known as pars dissipata) differs from the caudal part (pars compacta) in efferent connectivity, as rostrally located cholinergic neurons project to the dorsolateral striatum and substantia nigra pars compacta, whereas the caudally located ones project to the VTA and the dorsomedial striatum ( Martinez-Gonzalez et al, 2011 ).…”

Section: Discussionsupporting

confidence: 88%

Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit

Bayasgalan

Stupniki

Kovács

et al. 2021

Front. Cell. Neurosci.

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The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to the regulation of the sleep–wakefulness cycle. The M-current is a voltage-gated potassium current modulated mainly by cholinergic signaling. KCNQ subunits ensemble into ion channels responsible for the M-current. In the central nervous system, KCNQ4 expression is restricted to certain brainstem structures such as the RAS nuclei. Here, we investigated the presence and functional significance of KCNQ4 in the PPN by behavioral studies and the gene and protein expressions and slice electrophysiology using a mouse model lacking KCNQ4 expression. We found that this mouse has alterations in the adaptation to changes in light–darkness cycles, representing the potential role of KCNQ4 in the regulation of the sleep–wakefulness cycle. As cholinergic neurons from the PPN participate in the regulation of this cycle, we investigated whether the cholinergic PPN might also possess functional KCNQ4 subunits. Although the M-current is an electrophysiological hallmark of cholinergic neurons, only a subpopulation of them had KCNQ4-dependent M-current. Interestingly, the absence of the KCNQ4 subunit altered the expression patterns of the other KCNQ subunits in the PPN. We also determined that, in wild-type animals, the cholinergic inputs of the PPN modulated the M-current, and these in turn can modulate the level of synchronization between neighboring PPN neurons. Taken together, the KCNQ4 subunit is present in a subpopulation of PPN cholinergic neurons, and it may contribute to the regulation of the sleep–wakefulness cycle.

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“…This is based on the neurons having low threshold spiking, a transient outward potassium current (known as A-current), both of these properties, or none. In addition, it has also been found that cells with A-current can be either early or late firing (Baksa et al, 2019). The diversity in functional properties of cholinergic neurons is important as they are tonically firing and thus different characteristics could lead to different ACh release patterns, altering circuit activity.…”

Section: Genetic Diversity May Lead To Functional Subgroups In Cholinmentioning

confidence: 99%

New Insights Into Cholinergic Neuron Diversity

Ahmed

Knowles

Dehorter

2019

Front. Mol. Neurosci.

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Cholinergic neurons comprise a small population of cells in the striatum but have fundamental roles in fine tuning brain function, and in the etiology of neurological and psychiatric disorders such as Parkinson’s disease (PD) or schizophrenia. The process of developmental cell specification underlying neuronal identity and function is an area of great current interest. There has been significant progress in identifying the developmental origins, commonalities in molecular markers, and physiological properties of the cholinergic neurons. Currently, we are aware of a number of key factors that promote cholinergic fate during development. However, the extent of cholinergic cell diversity is still largely underestimated. New insights into the biological basis of their specification indicate that cholinergic neurons may be far more diverse than previously thought. This review article, highlights the physiological features and the synaptic properties that segregate cholinergic cell subtypes. It provides an accurate picture of cholinergic cell diversity underlying their organization and function in neuronal networks. This review article, also discusses current challenges in deciphering the logic of the cholinergic cell heterogeneity that plays a fundamental role in the control of neural processes in health and disease.

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Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus

Cited by 13 publications

References 70 publications

Simultaneously cholinergic projection in Ascending and Descending Circuits from Midbrain

Simultaneously cholinergic projection in Ascending and Descending Circuits from Midbrain

Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit

New Insights Into Cholinergic Neuron Diversity

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