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KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons.

Pérez-Ramírez MB, Laville A, Tapia D, Duhne M, Lara-González E, Bargas J, Galarraga E - Neural Plast. (2015)

Bottom Line: We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines 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.

View Article: PubMed Central - PubMed

Affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Suprathreshold responses of SPNs involve a G-protein coupled muscarinic component. (a), (b), Corticostriatal suprathreshold responses in a dSPN (a) and in an iSPN (b): 50 nM of the selective antagonist of muscarinic M1 class receptors, mamba toxin 7 (MT-7), reduced the amount of depolarization caused by the same stimulus in both neuron classes, indicating that endogenous ACh is necessary to reach these levels of depolarization during cortical stimulation. Colored traces: controls; black traces: during MT-7. ((c), (d)) Note that while activating with muscarine (1 μM), the opposite actions are obtained. There is an enhancement of evoked depolarization, thus adding to the action of endogenous ACh. ((e), (f)) Tukey box plots compare the area under the synaptic response (mVms) in both classes of SPNs, for MT-7 and muscarine applications.
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fig2: Suprathreshold responses of SPNs involve a G-protein coupled muscarinic component. (a), (b), Corticostriatal suprathreshold responses in a dSPN (a) and in an iSPN (b): 50 nM of the selective antagonist of muscarinic M1 class receptors, mamba toxin 7 (MT-7), reduced the amount of depolarization caused by the same stimulus in both neuron classes, indicating that endogenous ACh is necessary to reach these levels of depolarization during cortical stimulation. Colored traces: controls; black traces: during MT-7. ((c), (d)) Note that while activating with muscarine (1 μM), the opposite actions are obtained. There is an enhancement of evoked depolarization, thus adding to the action of endogenous ACh. ((e), (f)) Tukey box plots compare the area under the synaptic response (mVms) in both classes of SPNs, for MT-7 and muscarine applications.

Mentions: Here, we show evidence (Figure 2) that the response of SPNs to the same cortical stimulus is affected by activating muscarinic receptors. The same results can be obtained with perforated or nonperforated whole-cell recordings as well as with intracellular recordings [8]. Thus, Figures 2(a) and 2(b) show that the depolarization evoked by cortical stimulation was reduced in both classes of SPNs by blocking the activation of M1 receptors by the very selective mamba toxin 7 (50 nM MT-7) [46, 47]; indicating that G-protein coupled signaling activated by endogenous ACh was necessary to attain the level of depolarization to achieve repetitive firing [18]. After blockade of muscarinic M1 class receptors the area under the synaptic response of dSPNs decreased by 23% (from 16,510 ± 1,495 mVms to 12,690 ± 1,218 (mVms); ∗∗∗P < 0.0005; n = 12; Figure 2(e)) and the same actions were revealed for iSPNs: MT-7 decreased the area under the synaptic response by 22% (from 11,360 ± 809 mVms to 8,891 ± 853 mVms; ∗∗P < 0.0005; n = 9; Figure 2(e)). In both cases, firing was severely affected.


KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons.

Pérez-Ramírez MB, Laville A, Tapia D, Duhne M, Lara-González E, Bargas J, Galarraga E - Neural Plast. (2015)

Suprathreshold responses of SPNs involve a G-protein coupled muscarinic component. (a), (b), Corticostriatal suprathreshold responses in a dSPN (a) and in an iSPN (b): 50 nM of the selective antagonist of muscarinic M1 class receptors, mamba toxin 7 (MT-7), reduced the amount of depolarization caused by the same stimulus in both neuron classes, indicating that endogenous ACh is necessary to reach these levels of depolarization during cortical stimulation. Colored traces: controls; black traces: during MT-7. ((c), (d)) Note that while activating with muscarine (1 μM), the opposite actions are obtained. There is an enhancement of evoked depolarization, thus adding to the action of endogenous ACh. ((e), (f)) Tukey box plots compare the area under the synaptic response (mVms) in both classes of SPNs, for MT-7 and muscarine applications.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4465714&req=5

fig2: Suprathreshold responses of SPNs involve a G-protein coupled muscarinic component. (a), (b), Corticostriatal suprathreshold responses in a dSPN (a) and in an iSPN (b): 50 nM of the selective antagonist of muscarinic M1 class receptors, mamba toxin 7 (MT-7), reduced the amount of depolarization caused by the same stimulus in both neuron classes, indicating that endogenous ACh is necessary to reach these levels of depolarization during cortical stimulation. Colored traces: controls; black traces: during MT-7. ((c), (d)) Note that while activating with muscarine (1 μM), the opposite actions are obtained. There is an enhancement of evoked depolarization, thus adding to the action of endogenous ACh. ((e), (f)) Tukey box plots compare the area under the synaptic response (mVms) in both classes of SPNs, for MT-7 and muscarine applications.
Mentions: Here, we show evidence (Figure 2) that the response of SPNs to the same cortical stimulus is affected by activating muscarinic receptors. The same results can be obtained with perforated or nonperforated whole-cell recordings as well as with intracellular recordings [8]. Thus, Figures 2(a) and 2(b) show that the depolarization evoked by cortical stimulation was reduced in both classes of SPNs by blocking the activation of M1 receptors by the very selective mamba toxin 7 (50 nM MT-7) [46, 47]; indicating that G-protein coupled signaling activated by endogenous ACh was necessary to attain the level of depolarization to achieve repetitive firing [18]. After blockade of muscarinic M1 class receptors the area under the synaptic response of dSPNs decreased by 23% (from 16,510 ± 1,495 mVms to 12,690 ± 1,218 (mVms); ∗∗∗P < 0.0005; n = 12; Figure 2(e)) and the same actions were revealed for iSPNs: MT-7 decreased the area under the synaptic response by 22% (from 11,360 ± 809 mVms to 8,891 ± 853 mVms; ∗∗P < 0.0005; n = 9; Figure 2(e)). In both cases, firing was severely affected.

Bottom Line: We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines 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.

View Article: PubMed Central - PubMed

Affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus