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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

Blockade of KV7 channels is postsynaptic. (a) A pair of evoked excitatory postsynaptic currents (EPSCs) evoked from the cortex in a dSPN in the presence of bicuculline. (b) The decrease in conductance produced by XE991 produces a small decrease in EPSCs amplitude as detected at the soma. (c) Superimposition of (a) and (b). (d) Time course of amplitude changes in EPSC. (e) No significant change in the paired pulse ratio (PPR) was detected during the time of the experiment. (f) Tukey box plots showing that changes in PPR in the whole sample (n = 8) were no significant. (g) A pair of evoked EPSCs evoked from the cortex in an iSPN in the presence of bicuculline. (h) The decrease in conductance produced by XE991 produces a decrease in EPSCs amplitude as detected at the soma. (i) Superimposition of (g) and (h). (j) Time course of amplitude changes in EPSC. (k) No significant change in the paired pulse ratio (PPR) was detected. (l) Tukey box plots showing that changes in PPR, in the whole sample (n = 8), were no significant.
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fig8: Blockade of KV7 channels is postsynaptic. (a) A pair of evoked excitatory postsynaptic currents (EPSCs) evoked from the cortex in a dSPN in the presence of bicuculline. (b) The decrease in conductance produced by XE991 produces a small decrease in EPSCs amplitude as detected at the soma. (c) Superimposition of (a) and (b). (d) Time course of amplitude changes in EPSC. (e) No significant change in the paired pulse ratio (PPR) was detected during the time of the experiment. (f) Tukey box plots showing that changes in PPR in the whole sample (n = 8) were no significant. (g) A pair of evoked EPSCs evoked from the cortex in an iSPN in the presence of bicuculline. (h) The decrease in conductance produced by XE991 produces a decrease in EPSCs amplitude as detected at the soma. (i) Superimposition of (g) and (h). (j) Time course of amplitude changes in EPSC. (k) No significant change in the paired pulse ratio (PPR) was detected. (l) Tukey box plots showing that changes in PPR, in the whole sample (n = 8), were no significant.

Mentions: To see whether these effects on the synaptic corticostriatal response of SPNs had a presynaptic component or if all of them had a postsynaptic origin, we evoked pairs of EPSCs in control conditions in the presence of 10 μM bicuculline and these were compared to responses obtained in the presence of XE991. Figures 8(a) and 8(b) show a control recording in a dSPN (average in color and quantal variation in thin grey lines) and a recording in the presence of XE991, respectively. The superimposition is in Figure 8(c). There was a small decrease in current amplitude during the experiment as observed from the soma, suggesting again a decrease in membrane conductance in the region where the synaptic responses are generated (Figure 8(d)); however, there was no change in the paired pulse ratio (PPR; Figure 8(e)). Lack of significance in PPR changes is summarized in Figure 8(f) (n = 8). A similar experiment was performed in a sample of iSPNs (Figures 8(g)–8(l)). Here, the decrease in EPSC amplitude was larger suggesting that propagation in iSPNs dendrites is more important than in dSPNs dendrites, given that dendrites form the cell compartment where most synaptic inputs are generated [48, 50]. Nonetheless, changes in PPR were not significant (Figures 8(k) and 8(l)). It was concluded that XE991 reduced EPSCs amplitude in both SPNs without changing PPR and therefore, most actions observed were postsynaptic. In addition, it is known that M2–4 receptors, not M1 receptors, are located on presynaptic cortical glutamatergic terminals [10–13, 53].


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)

Blockade of KV7 channels is postsynaptic. (a) A pair of evoked excitatory postsynaptic currents (EPSCs) evoked from the cortex in a dSPN in the presence of bicuculline. (b) The decrease in conductance produced by XE991 produces a small decrease in EPSCs amplitude as detected at the soma. (c) Superimposition of (a) and (b). (d) Time course of amplitude changes in EPSC. (e) No significant change in the paired pulse ratio (PPR) was detected during the time of the experiment. (f) Tukey box plots showing that changes in PPR in the whole sample (n = 8) were no significant. (g) A pair of evoked EPSCs evoked from the cortex in an iSPN in the presence of bicuculline. (h) The decrease in conductance produced by XE991 produces a decrease in EPSCs amplitude as detected at the soma. (i) Superimposition of (g) and (h). (j) Time course of amplitude changes in EPSC. (k) No significant change in the paired pulse ratio (PPR) was detected. (l) Tukey box plots showing that changes in PPR, in the whole sample (n = 8), were no significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: Blockade of KV7 channels is postsynaptic. (a) A pair of evoked excitatory postsynaptic currents (EPSCs) evoked from the cortex in a dSPN in the presence of bicuculline. (b) The decrease in conductance produced by XE991 produces a small decrease in EPSCs amplitude as detected at the soma. (c) Superimposition of (a) and (b). (d) Time course of amplitude changes in EPSC. (e) No significant change in the paired pulse ratio (PPR) was detected during the time of the experiment. (f) Tukey box plots showing that changes in PPR in the whole sample (n = 8) were no significant. (g) A pair of evoked EPSCs evoked from the cortex in an iSPN in the presence of bicuculline. (h) The decrease in conductance produced by XE991 produces a decrease in EPSCs amplitude as detected at the soma. (i) Superimposition of (g) and (h). (j) Time course of amplitude changes in EPSC. (k) No significant change in the paired pulse ratio (PPR) was detected. (l) Tukey box plots showing that changes in PPR, in the whole sample (n = 8), were no significant.
Mentions: To see whether these effects on the synaptic corticostriatal response of SPNs had a presynaptic component or if all of them had a postsynaptic origin, we evoked pairs of EPSCs in control conditions in the presence of 10 μM bicuculline and these were compared to responses obtained in the presence of XE991. Figures 8(a) and 8(b) show a control recording in a dSPN (average in color and quantal variation in thin grey lines) and a recording in the presence of XE991, respectively. The superimposition is in Figure 8(c). There was a small decrease in current amplitude during the experiment as observed from the soma, suggesting again a decrease in membrane conductance in the region where the synaptic responses are generated (Figure 8(d)); however, there was no change in the paired pulse ratio (PPR; Figure 8(e)). Lack of significance in PPR changes is summarized in Figure 8(f) (n = 8). A similar experiment was performed in a sample of iSPNs (Figures 8(g)–8(l)). Here, the decrease in EPSC amplitude was larger suggesting that propagation in iSPNs dendrites is more important than in dSPNs dendrites, given that dendrites form the cell compartment where most synaptic inputs are generated [48, 50]. Nonetheless, changes in PPR were not significant (Figures 8(k) and 8(l)). It was concluded that XE991 reduced EPSCs amplitude in both SPNs without changing PPR and therefore, most actions observed were postsynaptic. In addition, it is known that M2–4 receptors, not M1 receptors, are located on presynaptic cortical glutamatergic terminals [10–13, 53].

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