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Global actions of nicotine on the striatal microcircuit.

Plata V, Duhne M, Pérez-Ortega J, Hernández-Martinez R, Rueda-Orozco P, Galarraga E, Drucker-Colín R, Bargas J - Front Syst Neurosci (2013)

Bottom Line: Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs.We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons.This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

View Article: PubMed Central - PubMed

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

ABSTRACT

The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

No MeSH data available.


Related in: MedlinePlus

Global actions of nicotine in the striatal circuit are blocked by mecamylamine. (A) Raster plot showing circuit activity in the presence of NMDA. Similarly to Figure 2A, left epoch shows activity with spontaneous synchronization of different neuron pools (colored dots). Middle epoch: nicotine (1 μM) added to the bath saline in the presence of NMDA induced a decrease in activity and the absence of color indicates that significant events of spontaneous synchronization are now absent. Right epoch: addition of 10 μM mecamylamine allowed the return of some peaks of synchronization showing that the activity of nicotine was receptor dependent (n = 3 slices; 6 epochs). (B) Activity histogram displaying multicellular activity from the raster plot above. Significant peaks of synchronization (colored) appear during NMDA. They disappeared when nicotine was added and reappeared after addition of mecamylamine to the bath saline. (C) Cumulative activity taken from histogram in (B) shows that rate of accumulated activity was significantly lower in the presence of nicotine plus NMDA than with NMDA alone. It is also shown that mecamylamine virtually restored the level of accumulated activity over time in the continuous presence of both NMDA and nicotine. (D) Matrix of vectors similarity along time reassured that activity in NMDA is due to network activity. (E) Histogram showing that the number of peaks of synchronization per epoch decreased significantly when nicotine was added in the presence of NMDA-induced activity (***P < 0.001) and then increased again, significantly (**P < 0.01), when mecamylamine was added in the presence of nicotine.
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Figure 3: Global actions of nicotine in the striatal circuit are blocked by mecamylamine. (A) Raster plot showing circuit activity in the presence of NMDA. Similarly to Figure 2A, left epoch shows activity with spontaneous synchronization of different neuron pools (colored dots). Middle epoch: nicotine (1 μM) added to the bath saline in the presence of NMDA induced a decrease in activity and the absence of color indicates that significant events of spontaneous synchronization are now absent. Right epoch: addition of 10 μM mecamylamine allowed the return of some peaks of synchronization showing that the activity of nicotine was receptor dependent (n = 3 slices; 6 epochs). (B) Activity histogram displaying multicellular activity from the raster plot above. Significant peaks of synchronization (colored) appear during NMDA. They disappeared when nicotine was added and reappeared after addition of mecamylamine to the bath saline. (C) Cumulative activity taken from histogram in (B) shows that rate of accumulated activity was significantly lower in the presence of nicotine plus NMDA than with NMDA alone. It is also shown that mecamylamine virtually restored the level of accumulated activity over time in the continuous presence of both NMDA and nicotine. (D) Matrix of vectors similarity along time reassured that activity in NMDA is due to network activity. (E) Histogram showing that the number of peaks of synchronization per epoch decreased significantly when nicotine was added in the presence of NMDA-induced activity (***P < 0.001) and then increased again, significantly (**P < 0.01), when mecamylamine was added in the presence of nicotine.

Mentions: The sequence of peaks of synchronization in the activity histogram denotes the activity of the microcircuit along time, that is, a sequence of neuron pools synchronizing their firing and alternating their activity with other neuron pools. This type of circuit behavior has been called assembly dynamics (e.g., Carrillo-Reid et al., 2008). To know whether synchronization increased or decreased after a given treatment, the number of neuronal vectors was counted in each of several image sequences (epochs) at different times in the same experiment. Mean of averages from different slices were lumped together and a free-distribution statistic was employed (Mann-Whitney's U) for comparison. A Wilcoxon T-test was used to compare the same slice under different conditions. Note that each 3 min epoch commonly has dozens of individual cells. For comparison of epochs from different slices (Figure 3) the Kruskal-Wallis one way analysis of variance was used with post hoc Dunn tests.


Global actions of nicotine on the striatal microcircuit.

Plata V, Duhne M, Pérez-Ortega J, Hernández-Martinez R, Rueda-Orozco P, Galarraga E, Drucker-Colín R, Bargas J - Front Syst Neurosci (2013)

Global actions of nicotine in the striatal circuit are blocked by mecamylamine. (A) Raster plot showing circuit activity in the presence of NMDA. Similarly to Figure 2A, left epoch shows activity with spontaneous synchronization of different neuron pools (colored dots). Middle epoch: nicotine (1 μM) added to the bath saline in the presence of NMDA induced a decrease in activity and the absence of color indicates that significant events of spontaneous synchronization are now absent. Right epoch: addition of 10 μM mecamylamine allowed the return of some peaks of synchronization showing that the activity of nicotine was receptor dependent (n = 3 slices; 6 epochs). (B) Activity histogram displaying multicellular activity from the raster plot above. Significant peaks of synchronization (colored) appear during NMDA. They disappeared when nicotine was added and reappeared after addition of mecamylamine to the bath saline. (C) Cumulative activity taken from histogram in (B) shows that rate of accumulated activity was significantly lower in the presence of nicotine plus NMDA than with NMDA alone. It is also shown that mecamylamine virtually restored the level of accumulated activity over time in the continuous presence of both NMDA and nicotine. (D) Matrix of vectors similarity along time reassured that activity in NMDA is due to network activity. (E) Histogram showing that the number of peaks of synchronization per epoch decreased significantly when nicotine was added in the presence of NMDA-induced activity (***P < 0.001) and then increased again, significantly (**P < 0.01), when mecamylamine was added in the presence of nicotine.
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Related In: Results  -  Collection

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Figure 3: Global actions of nicotine in the striatal circuit are blocked by mecamylamine. (A) Raster plot showing circuit activity in the presence of NMDA. Similarly to Figure 2A, left epoch shows activity with spontaneous synchronization of different neuron pools (colored dots). Middle epoch: nicotine (1 μM) added to the bath saline in the presence of NMDA induced a decrease in activity and the absence of color indicates that significant events of spontaneous synchronization are now absent. Right epoch: addition of 10 μM mecamylamine allowed the return of some peaks of synchronization showing that the activity of nicotine was receptor dependent (n = 3 slices; 6 epochs). (B) Activity histogram displaying multicellular activity from the raster plot above. Significant peaks of synchronization (colored) appear during NMDA. They disappeared when nicotine was added and reappeared after addition of mecamylamine to the bath saline. (C) Cumulative activity taken from histogram in (B) shows that rate of accumulated activity was significantly lower in the presence of nicotine plus NMDA than with NMDA alone. It is also shown that mecamylamine virtually restored the level of accumulated activity over time in the continuous presence of both NMDA and nicotine. (D) Matrix of vectors similarity along time reassured that activity in NMDA is due to network activity. (E) Histogram showing that the number of peaks of synchronization per epoch decreased significantly when nicotine was added in the presence of NMDA-induced activity (***P < 0.001) and then increased again, significantly (**P < 0.01), when mecamylamine was added in the presence of nicotine.
Mentions: The sequence of peaks of synchronization in the activity histogram denotes the activity of the microcircuit along time, that is, a sequence of neuron pools synchronizing their firing and alternating their activity with other neuron pools. This type of circuit behavior has been called assembly dynamics (e.g., Carrillo-Reid et al., 2008). To know whether synchronization increased or decreased after a given treatment, the number of neuronal vectors was counted in each of several image sequences (epochs) at different times in the same experiment. Mean of averages from different slices were lumped together and a free-distribution statistic was employed (Mann-Whitney's U) for comparison. A Wilcoxon T-test was used to compare the same slice under different conditions. Note that each 3 min epoch commonly has dozens of individual cells. For comparison of epochs from different slices (Figure 3) the Kruskal-Wallis one way analysis of variance was used with post hoc Dunn tests.

Bottom Line: Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs.We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons.This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

View Article: PubMed Central - PubMed

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

ABSTRACT

The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

No MeSH data available.


Related in: MedlinePlus