Striatal cholinergic interneurons and Parkinson's disease

Tanimura, Akio; Pancani, Tristano; Lim, Sean Austin O.; Tubert, Cecilia; Melendez, Alexandra E.; Shen, Weisen; Surmeier, D. James

doi:10.1111/ejn.13638

Cited by 75 publications

(87 citation statements)

References 202 publications

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“…Although the importance of cholinergic signaling through mAChRs to the striatal imbalance and PD symptoms has long been recognized (Lim et al, 2014;Pisani et al, 2007;Tanimura et al, 2018), the importance of nAChRs has not. Our studies demonstrate that nAChRs contribute to the PD state itself, showing that either chemogenetic suppression of the PFn pathway or KD of a6 mRNA in the PFn alleviate motor-learning deficits accompanying the parkinsonian state in mice.…”

Section: Signaling Through Nachrs Contributed To Pd Symptomsmentioning

confidence: 99%

“…For example, like cortical neurons, CLn neurons form axospinous synapses on both iSPNs and dSPNs, whereas PFn neurons form axodendritic synapses on SPNs (Lacey et al, 2007;Smith et al, 2009). In addition, PFn, but not CLn, neurons robustly innervate giant aspiny cholinergic interneurons (ChIs), which then modulate a wide range of targets within the striatum, including SPNs (Consolo et al, 1996;Guo et al, 2015;Lapper and Bolam, 1992;Tanimura et al, 2018). The PFn-ChI network has been hypothesized to ''reset'' the corticostriatal circuitry in response to salient environmental events and to promote set-shifting (Bradfield et al, 2013;Brown et al, 2010;Ding et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal Indirect Pathway Neurons in Parkinson’s Disease Models

Tanimura

Kondapalli

et al. 2019

Neuron

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113

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Graphical Abstract Highlights d Thalamic neurons more potently activated indirect pathway striatal neurons in PD mice d This amplification was dependent upon striatal cholinergic interneurons (ChIs) d ChI-activated, presynaptic nicotinic receptors increased thalamic glutamate release d Suppressing this signaling pathway restored motor learning in PD mice SUMMARYThe motor symptoms of Parkinson's disease (PD) are thought to stem from an imbalance in the activity of striatal direct-and indirect-pathway spiny projection neurons (SPNs). Disease-induced alterations in the activity of networks controlling SPNs could contribute to this imbalance. One of these networks is anchored by the parafascicular nucleus (PFn) of the thalamus. To determine the role of the PFn in striatal PD pathophysiology, optogenetic, chemogenetic, and electrophysiological tools were used in ex vivo slices from transgenic mice with regionspecific Cre recombinase expression. These studies revealed that in parkinsonian mice, the functional connectivity of PFn neurons with indirect pathway SPNs (iSPNs) was selectively enhanced by cholinergic interneurons acting through presynaptic nicotinic acetylcholine receptors (nAChRs) on PFn terminals. Attenuating this network adaptation by chemogenetic or genetic strategies alleviated motor-learning deficits in parkinsonian mice, pointing to a potential new therapeutic strategy for PD patients. to D.J.S.

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Section: Signaling Through Nachrs Contributed To Pd Symptomsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal Indirect Pathway Neurons in Parkinson’s Disease Models

Tanimura

Kondapalli

et al. 2019

Neuron

Self Cite

113

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“…The elevation of cholinergic signaling in PD is directly related to the alterations in ChI spiking (Tanimura et al., ). As described before, M 4 autoreceptors in ChIs slow firing rate and ACh release (Zhang et al., ).…”

Section: Movement Disorders Related To Cholinergic Interneuronsmentioning

confidence: 99%

Cholinergic modulation of striatal microcircuits

Abudukeyoumu

Hernández-Flores

García‐Muñoz

et al. 2018

Eur J of Neuroscience

100

107

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The purpose of this review is to bridge the gap between earlier literature on striatal cholinergic interneurons and mechanisms of microcircuit interaction demonstrated with the use of newly available tools. It is well known that the main source of the high level of acetylcholine in the striatum, compared to other brain regions, is the cholinergic interneurons. These interneurons provide an extensive local innervation that suggests they may be a key modulator of striatal microcircuits. Supporting this idea requires the consideration of functional properties of these interneurons, their influence on medium spiny neurons, other interneurons, and interactions with other synaptic regulators. Here, we underline the effects of intrastriatal and extrastriatal afferents onto cholinergic interneurons and discuss the activation of pre- and postsynaptic muscarinic and nicotinic receptors that participate in the modulation of intrastriatal neuronal interactions. We further address recent findings about corelease of other transmitters in cholinergic interneurons and actions of these interneurons in striosome and matrix compartments. In addition, we summarize recent evidence on acetylcholine-mediated striatal synaptic plasticity and propose roles for cholinergic interneurons in normal striatal physiology. A short examination of their role in neurological disorders such as Parkinson's, Huntington's, and Tourette's pathologies and dystonia is also included.

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“…1J-K). The strength of rhythmic firing, quantified based on auto-correlation peaks in the theta band (Theta Index, see Methods), was correlated with the length of the refractory period (p = 0.0028), suggesting a cell-autonomous mechanism, similar to striatal cholinergic interneurons 47 and regular firing dopaminergic neurons 48 .…”

Section: Distinct Firing Patterns Of Cholinergic Neurons In Vivomentioning

confidence: 99%

Distinct synchronization, cortical coupling and behavioural function of two basal forebrain cholinergic neuron types

Laszlovszky

Schlingloff

Freund

et al. 2019

Preprint

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Basal forebrain cholinergic neurons (BFCN) densely innervate the forebrain and modulate synaptic plasticity, cortical processing, brain states and oscillations. However, little is known about the functional diversity of cholinergic neurons and whether distinct types support different functions. To examine this question we recorded BFCN in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCN that markedly differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (BFCNBURST) fired in zero-lag synchrony with each other, phase-locked to cortical theta activity and fired precisely timed bursts of action potentials after reward and punishment. Regular firing cholinergic neurons (BFCNREG) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity (5-10 Hz), fired asynchronously with each other and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of BFCNBURST neurons to auditory cortex predicted the timing of mouse responses, whereas tone-evoked cortical coupling of BFCNREG predicted correct detections. We propose that cortical activation relevant for behavior is controlled by the balance of two cholinergic cell types, where the precise proportion of the strongly activating BFCNBURST follows an anatomical gradient along the antero-posterior axis of the basal forebrain.

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Striatal cholinergic interneurons and Parkinson's disease

Cited by 75 publications

References 202 publications

Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal Indirect Pathway Neurons in Parkinson’s Disease Models

Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal Indirect Pathway Neurons in Parkinson’s Disease Models

Cholinergic modulation of striatal microcircuits

Distinct synchronization, cortical coupling and behavioural function of two basal forebrain cholinergic neuron types

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