Modulation of direct pathway striatal projection neurons by muscarinic M4-type receptors

Hernández-Flores, Teresa; Hernández-González, Omar; Perez-Ramirez, María Belén; Lara-González, Esther; Arias-García, Mario A.; Duhne, Mariana; Perez-Burgos, Azucena; Prieto, G. Aleph; Figueroa, Alejandra; Galarraga, Elvira; Bargas, José

doi:10.1016/j.neuropharm.2014.09.028

Cited by 45 publications

(74 citation statements)

References 74 publications

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“…A suprathreshold stimulus may activate SPNs directly and indirectly through the polysynaptic activation of interneurons and other SPNs [1, 42]. Besides activating glutamatergic and GABAergic receptors, polysynaptic responses last hundreds of milliseconds and include the activation of muscarinic receptors as well as several classes of intrinsic voltage dependent currents [24, 26, 43, 44]. This multisynaptic and convergent activation is one origin of “down”- to “up”-states voltage transitions [7].…”

Section: Resultsmentioning

confidence: 99%

“…It has been shown that cholinergic neurons respond with a slightly briefer latency than the responses of SPNs [1, 24]. In addition, continuous firing of cholinergic interneurons maintains a tonic level of ACh in the striatum [7, 24, 45], muscarinic M 1 receptors are expressed in all SPNs, and K V 7 channels have been shown to compose a minor but functionally important part of the intrinsic voltage gated currents that are present in all SPNs [34]. …”

Section: Resultsmentioning

confidence: 99%

“…Modulation lasted the whole duration of the responses and it does not appear to be saturated since muscarinic actions could add to the endogenous ACh actions. Apparently, the activation of muscarinic receptors may produce changes in passive properties (e.g., electrotonic decay and membrane resistance) in the membrane compartment where most synaptic inputs are generated (mostly secondary and tertiary dendrites) and on intrinsic currents that become activated during synaptic suprathreshold depolarization [24, 26] to explain the changes in amplitude of these responses.…”

Section: Resultsmentioning

confidence: 99%

“…But these actions were due to muscarinic M 4 class receptors that appeared to act only in dSPNs [24]. In addition, modulation of Ca 2+ -activated K + -currents shunts the trains of action potentials generated in iSPNs making them briefer than those generated in dSPNs [26].…”

Section: Resultsmentioning

confidence: 99%

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KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

et al. 2015

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Striatal projection neurons (SPNs) process motor and cognitive information. Their activity is affected by Parkinson's disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

et al. 2015

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“…Impacting these other systems may ameliorate TD through addressing this imbalance (and possibly a direct effect in some instances); it is known, for example, that there is a complex interplay between dopamine and a number of other neurotransmitters including GABA, glutamate, serotonin and acetylcholine [55,[63][64][65][66]. If we use acetylcholine as an example, it interacts with dopamine at the level of the striatum in a complex fashion that is still being detailed and, in addition, engages other systems [65,66]. The imbalance between dopamine and acetylcholine is well established in Parkinson's disease as well as AP-related parkinsonism; interestingly, parkinsonism has been identified as a risk factor in TD [67], as has the use of anticholinergic agents [3].…”

Section: Other Systemsmentioning

confidence: 99%

Emerging drugs for antipsychotic-induced tardive dyskinesia: investigational drugs in Phase II and Phase III clinical trials

Lockwood

Remington

2015

Expert Opinion on Emerging Drugs

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Striatal Cholinergic Interneurons Control Physical Nicotine Withdrawal via Muscarinic Receptor Signaling

Kim,

Woo

et al. 2024

Advanced Science

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Striatal cholinergic interneurons (ChIs) provide acetylcholine tone to the striatum and govern motor functions. Nicotine withdrawal elicits physical symptoms that dysregulate motor behavior. Here, the role of striatal ChIs in physical nicotine withdrawal is investigated. Mice under RNAi‐dependent genetic inhibition of striatal ChIs (ChIGI) by suppressing the sodium channel subunit NaV1.1, lessening action potential generation and activity‐dependent acetylcholine release is first generated. ChIGI markedly reduced the somatic signs of nicotine withdrawal without affecting other nicotine‐dependent or striatum‐associated behaviors. Multielectrode array (MEA) recording revealed that ChIGI reversed ex vivo nicotine‐induced alterations in the number of neural population spikes in the dorsal striatum. Notably, the drug repurposing strategy revealed that a clinically‐approved antimuscarinic drug, procyclidine, fully mimicked the therapeutic electrophysiological effects of ChIGI. Furthermore, both ChIGI and procyclidine prevented the nicotine withdrawal‐induced reduction in striatal dopamine release in vivo. Lastly, therapeutic intervention with procyclidine dose‐dependently diminished the physical signs of nicotine withdrawal. The data demonstrated that the striatal ChIs are a critical substrate of physical nicotine withdrawal and that muscarinic antagonism holds therapeutic potential against nicotine withdrawal.

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Modulation of direct pathway striatal projection neurons by muscarinic M4-type receptors

Cited by 45 publications

References 74 publications

KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

Emerging drugs for antipsychotic-induced tardive dyskinesia: investigational drugs in Phase II and Phase III clinical trials

Striatal Cholinergic Interneurons Control Physical Nicotine Withdrawal via Muscarinic Receptor Signaling

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