Peripheral type of choline acetyltransferase: Biological and evolutionary implications for novel mechanisms in cholinergic system

Bellier, Jean-Pierre; Kimura, Hiroshi

doi:10.1016/j.jchemneu.2011.02.005

Cited by 44 publications

(34 citation statements)

References 149 publications

(189 reference statements)

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“…Intramedullary pChAT-IR neurons, supplying adrenal cortex and medulla, belong to the postganglionic autonomic system and may therefore be both the source of sympathetic and parasympathetic postganglionic fibers, as well as providing one of the targets of the extrinsic adrenal innervation. In agreement, Bellier and Kimura (2011), based on previous studies, suggested that ACh could be released directly from the centripetal and centrifugal pChAT-containing nerves implying that pChAT may function within axons or presynaptic terminals.…”

Section: Discussionsupporting

confidence: 88%

“…The conventional ChAT protein was called ChAT of the common type (cChAT). Although the antibody against pChAT is capable of detecting some positive neurons in the central nervous system (Kanayama et al, 2003;Yasuhara et al, 2003), pChAT immunohistochemistry proves to be a powerful tool to visualize peripheral cholinergic structures (Nakanishi et al, 1999;Nakajima et al, 2000;Chiocchetti et al, 2003;Yasuhara et al, 2004Yasuhara et al, , 2007Yasuhara et al, , 2008 and it is accepted now to be one of the ACh synthesizing enzymes by Bellier and Kimura (2011) who suggested that pChAT may utilize a new catalytic center alternative to His 334 . They added, all neurons contained pChAT, and extracted pChAT showed sufficient enzyme activity to produce physiological concentrations of ACh.…”

Section: Introductionmentioning

confidence: 99%

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Expression and localization of pChAT as a novel method to study cholinergic innervation of rat adrenal gland

Elnasharty

Sayed-Ahmed

2014

Acta Histochemica

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Expression and localization of pChAT as a novel method to study cholinergic innervation of rat adrenal gland

Elnasharty

Sayed-Ahmed

2014

Acta Histochemica

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“…ChAT isoforms have also been identified in other species (51, 52), such as the pChAT splice variant of rats specific to the peripheral nervous system (53). The catalytical activity rate of ChAT is ∼3,000-fold greater than that of pChAT (54,55). Conceivably, zebrafish ChATa and ChATb could differ in their rate or efficiency of ACh synthesis.…”

Section: Resultsmentioning

confidence: 99%

Cholinergic left-right asymmetry in the habenulo-interpeduncular pathway

Hong

Santhakumar

Akitake

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The habenulo-interpeduncular pathway, a highly conserved cholinergic system, has emerged as a valuable model to study leftright asymmetry in the brain. In larval zebrafish, the bilaterally paired dorsal habenular nuclei (dHb) exhibit prominent left-right differences in their organization, gene expression, and connectivity, but their cholinergic nature was unclear. Through the discovery of a duplicated cholinergic gene locus, we now show that choline acetyltransferase and vesicular acetylcholine transporter homologs are preferentially expressed in the right dHb of larval zebrafish. Genes encoding the nicotinic acetylcholine receptor subunits α2 and β4 are transcribed in the target interpeduncular nucleus (IPN), suggesting that the asymmetrical cholinergic pathway is functional. To confirm this, we activated channelrhodopsin-2 specifically in the larval dHb and performed whole-cell patchclamp recording of IPN neurons. The response to optogenetic or electrical stimulation of the right dHb consisted of an initial fast glutamatergic excitatory postsynaptic current followed by a slowrising cholinergic current. In adult zebrafish, the dHb are divided into discrete cholinergic and peptidergic subnuclei that differ in size between the left and right sides of the brain. After exposing adults to nicotine, fos expression was activated in subregions of the IPN enriched for specific nicotinic acetylcholine receptor subunits. Our studies of the newly identified cholinergic gene locus resolve the neurotransmitter identity of the zebrafish habenular nuclei and reveal functional asymmetry in a major cholinergic neuromodulatory pathway of the vertebrate brain.ateralization of brain function is found throughout the animal kingdom, yet knowledge of the underlying neural bases for left-right (L-R) specializations is limited. Multiple developmental mechanisms could account for differential neural activity, including asymmetry in cell number or density, in specification of neuronal types, or in connectivity. Increasing evidence suggests that L-R differences in neurotransmitter distribution also play an important role in lateralized behaviors.The bilaterally paired habenular nuclei (Hb) of zebrafish provide a valuable model to study brain asymmetry. In larvae, the dorsal habenulae (dHb) [equivalent to medial habenular nuclei (mHb) of mammals] exhibit pronounced L-R differences in size, molecular properties, and connections with their midbrain target, the interpeduncular nucleus (IPN) (1-3). The Hb-IPN pathway connects limbic areas of the forebrain and midbrain (4), and has been implicated in nicotine addiction in mammals (5).The mHb-IPN tract is a major cholinergic system across vertebrates (6-11); however, it is still unresolved whether this pathway is cholinergic in zebrafish. Cholinergic neurons are defined by the presence of choline acetyltransferase (ChAT), which synthesizes ACh from choline and acetyl CoA, and vesicular acetylcholine transporter (VAChT), which packages ACh into synaptic vesicles. The chat and vacht genes are situa...

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“…Indeed, it has been shown by the group of Kimura that there are two splice variants of the ChAT enzyme, one expressed in the CNS and termed ''common'' (cChAT) and one expressed predominantly in the PNS and termed ''peripheral'' (pChAT; Bellier and Kimura, 2011;Tooyama and Kimura, 2000). The main difference between the two forms of ChAT resides in the fact that pChAT lacks exons 6-9 (Tooyama and Kimura, 2000).…”

Section: Dorsal Horn Cholinergic Interneurons: Morphological Neurochmentioning

confidence: 99%

Morphological and functional characterization of cholinergic interneurons in the dorsal horn of the mouse spinal cord

Mesnage

Gaillard

Godin

et al. 2011

J of Comparative Neurology

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Endogenous acetylcholine is an important modulator of sensory processing, especially at the spinal level, where nociceptive (pain-related) stimuli enter the central nervous system and are integrated before being relayed to the brain. To decipher the organization of the local cholinergic circuitry in the spinal dorsal horn, we used transgenic mice expressing enchanced green fluorescent protein specifically in cholinergic neurons (ChAT::EGFP) and characterized the morphology, neurochemistry, and firing properties of the sparse population of cholinergic interneurons in this area. Three-dimensional reconstruction of lamina III ChAT::EGFP neurons based either on their intrinsic fluorescence or on intracellular labeling in live tissue demonstrated that these neurons have long and thin processes that grow preferentially in the dorsal direction. Their dendrites and axon are highly elongated in the rostrocaudal direction, beyond the limits of a single spinal segment. These unique morphological features suggest that dorsal horn cholinergic interneurons are the main contributors to the plexus of cholinergic processes located in lamina IIi, just dorsal to their cell bodies. In addition, immunostainings demonstrated that dorsal horn cholinergic interneurons in the mouse are γ-aminobutyric acidergic and express nitric oxide synthase, as in rats. Finally, electrophysiological recordings from these neurons in spinal cord slices demonstrate that two-thirds of them have a repetitive spiking pattern with frequent rebound spikes following hyperpolarization. Altogether our results indicate that, although they are rare, the morphological and functional features of cholinergic neurons enable them to collect segmental information in superficial layers of the dorsal horn and to modulate it over several segments.

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Peripheral type of choline acetyltransferase: Biological and evolutionary implications for novel mechanisms in cholinergic system

Cited by 44 publications

References 149 publications

Expression and localization of pChAT as a novel method to study cholinergic innervation of rat adrenal gland

Expression and localization of pChAT as a novel method to study cholinergic innervation of rat adrenal gland

Cholinergic left-right asymmetry in the habenulo-interpeduncular pathway

Morphological and functional characterization of cholinergic interneurons in the dorsal horn of the mouse spinal cord

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