Cholinergic Suppression of KCNQ Channel Currents Enhances Excitability of Striatal Medium Spiny Neurons

Shen, Weisen; Hamilton, Susan; Nathanson, Neil M.; Surmeíer, D. James

doi:10.1523/jneurosci.1381-05.2005

Cited by 201 publications

(178 citation statements)

References 78 publications

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“…Previous work by our group has verified that neurons identified in this way have the appropriate gene expression profile, as well as typical anatomical and physiological features of MSNs (Shen et al, 2005;Day et al, 2006). Although the estimate of connectivity between D 2 MSNs and between D 1 MSNs relied on detection of a positive phenotypic marker, our estimates of connectivity between D 2 and D 1 MSNs relied on recording from an MSN that appeared not to express EGFP in BAC D 2 tissue.…”

Section: Msns Are Not Randomly Coupledmentioning

confidence: 83%

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Taverna

Ilijić²,

Surmeier³

2008

J. Neurosci.

359

460

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Section: Msns Are Not Randomly Coupledmentioning

confidence: 83%

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Taverna

Ilijić²,

Surmeier³

2008

J. Neurosci.

359

460

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“…The gating changes introduced by the KCNQ2 A/V mutation herein investigated and, in particular, the novel dependence of current activation kinetics on the prepulse voltage, suggest that the mutation-induced functional derangement of I KM may more prominently affect those neurons, such as GABAergic interneurons, firing at relatively high frequencies and whose resting membrane potential is more depolarized and closer to the threshold for spike initiation. The recent observation that, in hippocampal (Lawrence et al, 2006), striatal (Shen et al 2005), and cerebellar (Forti et al, 2006) GABAergic interneurons, I KM controls interspike interval, firing frequency, and overall network excitability, seems to lend support to this hypothesis. Moreover, during the first weeks of postnatal life, GABAergic neurons undergo age-dependent developmental switching from excitatory to inhibitory (Owens et al, 1996), suggesting that, in addition to changes in intrinsic excitability, also neuronal synchronization by excitatory synaptic activity may participate in BFNC pathogenesis (Okada et al, 2003); mutation-induced enhanced excitatory drive may ultimately lead to network hyperexcitability, thus predisposing to BFNC.…”

Section: Discussionmentioning

confidence: 94%

Atypical Gating Of M-Type Potassium Channels Conferred by Mutations in Uncharged Residues in the S₄Region of KCNQ2 Causing Benign Familial Neonatal Convulsions

Soldovieri¹,

Cilio²,

Miceli³

et al. 2007

J. Neurosci.

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Heteromeric assembly of KCNQ2 and KCNQ3 subunits underlie the M-current (I KM ), a slowly activating and noninactivating neuronal K ϩ current. Mutations in KCNQ2 and KCNQ3 genes cause benign familial neonatal convulsions (BFNCs), a rare autosomal-dominant epilepsy of the newborn. In the present study, we describe the identification of a novel KCNQ2 heterozygous mutation (c587t) in a BFNC-affected family, leading to an alanine to valine substitution at amino acid position 196 located at the N-terminal end of the voltage-sensing S 4 domain. The consequences on KCNQ2 subunit function prompted by the A196V substitution, as well as by the A196V/L197P mutation previously described in another BFNC-affected family, were investigated by macroscopic and single-channel current measurements in CHO cells transiently transfected with wild-type and mutant subunits. When compared with KCNQ2 channels, homomeric KCNQ2 A196V or A196V/L197P channels showed a 20 mV rightward shift in their activation voltage dependence, with no concomitant change in maximal open probability or single-channel conductance. Furthermore, current activation kinetics of KCNQ2 A196V channels displayed an unusual dependence on the conditioning prepulse voltage, being markedly slower when preceded by prepulses to more depolarized potentials. Heteromeric channels formed by KCNQ2 A196V and KCNQ3 subunits displayed gating changes similar to those of KCNQ2 A196V homomeric channels. Collectively, these results reveal a novel role for noncharged residues in the N-terminal end of S 4 in controlling gating of I KM and suggest that gating changes caused by mutations at these residues may decrease I KM function, thus causing neuronal hyperexcitability, ultimately leading to neonatal convulsions.

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“…ACh acts through muscarinic receptors present on MSNs to decrease the activity of KCNQ (M-current) and Kir2.3 channels, thereby increasing MSN excitability (54,55). In addition, ACh also works through muscarinic receptors to inhibit the release of glutamate from corticostriatal terminals and GABA from striatal FS cells (51,56).…”

Section: M1 Superficialmentioning

confidence: 99%

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Kondabolu

Roberts

Bucklin

et al. 2016

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

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Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonianlike motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms.E xaggerated beta oscillations (15-30 Hz) within the cortico-basal ganglia-thalamic (CBT) neural network are putative electrophysiological correlates of bradykinesia and rigidity in Parkinson's disease (PD) (1-4). Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4, 5). Beta oscillations are also found in the CBT circuits of patients with other movement-related disorders, such as epilepsy and dystonia (6, 7), and in normal, nonhuman primates (8, 9) and normal rodents (10, 11). Moreover, brief elevations (≤200 ms) of beta oscillations are observed in the basal ganglia of task-performing nonhuman primates and rodents during specific phases of behavioral tasks (10, 12, 13), indicating that beta oscillations may be important for motor and nonmotor functions. In contrast to the regulated temporal variability of beta oscillations in normal motor functions, temporal stability is correlated with the parkinsonian motor symptoms of bradykinesia and rigidity (2). Together, these findings suggest that brief epochs of beta oscillations are a normal aspect of basal ganglia dynamics, their temporal modulation is important for movement regulation, and loss of regulation or uncontrolled expression of beta oscillations may contribute to movement deficits, such as those observed in PD.Despite the clear link bet...

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Cholinergic Suppression of KCNQ Channel Currents Enhances Excitability of Striatal Medium Spiny Neurons

Cited by 201 publications

References 78 publications

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Atypical Gating Of M-Type Potassium Channels Conferred by Mutations in Uncharged Residues in the S₄Region of KCNQ2 Causing Benign Familial Neonatal Convulsions

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

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Cholinergic Suppression of KCNQ Channel Currents Enhances Excitability of Striatal Medium Spiny Neurons

Cited by 201 publications

References 78 publications

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

Atypical Gating Of M-Type Potassium Channels Conferred by Mutations in Uncharged Residues in the S4Region of KCNQ2 Causing Benign Familial Neonatal Convulsions

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

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Atypical Gating Of M-Type Potassium Channels Conferred by Mutations in Uncharged Residues in the S₄Region of KCNQ2 Causing Benign Familial Neonatal Convulsions