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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

Assembly dynamics in the control striatal circuitry after NMDA. (A) Raster plot showing the simultaneous activity of >100 neurons in a striatal slice using calcium-imaging. Each row in the matrix represents the activity of a single neuron across the series of images (columns). Left epoch shows 3 min of activity in control striatal tissue without NMDA. Note scarce activity and the absence of peaks of synchronization. In the next three epochs, separated by dashed vertical lines, 9 min of activity are shown after adding 2 μM NMDA into the bath saline (denoted by horizontal black line on top). Note that many more dots, some of them colored, populate the matrix. Colored dots denote the synchronized activity of several neurons in a given column or neighboring columns (a neuron pool is then represented as a column vector). Note that different neuron pools produce the circuit activity along time. (B) Activity histogram at bottom is the summed neuronal activity (multicellular activity) from the raster plot above column by column (frame by frame in a given movie). The dashed line shows the level of significance for the spontaneous peaks of synchronization denoted by colors (obtained by Monte Carlo simulations; statistically significant neuronal vectors; n = 6 slices). (C) A similarity index matrix compares each vector with all others along time: a patchy appearance shows that similar vectors were in charge of activity. (D) Dimensionality reduction using locally linear embedding (LLE) shows neuronal vectors projected in a two dimensional space with no units. Similar vectors grouped together (denoted by different colors) give raise to network states. The transitions among network states are denoted by arrows. Percentages give the probability to leave a given state. Colored dots and arrows represent the sequential activity of the circuit, that is, pools of neurons synchronized their firing and pass their activity from one pool of neurons to the other: cell assembly dynamics (Carrillo-Reid et al., 2008). Note reverberant trajectories in the sequence. Here and in the next figures, epochs (times of continuous image series) are separated by vertical dashed lines.
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Figure 1: Assembly dynamics in the control striatal circuitry after NMDA. (A) Raster plot showing the simultaneous activity of >100 neurons in a striatal slice using calcium-imaging. Each row in the matrix represents the activity of a single neuron across the series of images (columns). Left epoch shows 3 min of activity in control striatal tissue without NMDA. Note scarce activity and the absence of peaks of synchronization. In the next three epochs, separated by dashed vertical lines, 9 min of activity are shown after adding 2 μM NMDA into the bath saline (denoted by horizontal black line on top). Note that many more dots, some of them colored, populate the matrix. Colored dots denote the synchronized activity of several neurons in a given column or neighboring columns (a neuron pool is then represented as a column vector). Note that different neuron pools produce the circuit activity along time. (B) Activity histogram at bottom is the summed neuronal activity (multicellular activity) from the raster plot above column by column (frame by frame in a given movie). The dashed line shows the level of significance for the spontaneous peaks of synchronization denoted by colors (obtained by Monte Carlo simulations; statistically significant neuronal vectors; n = 6 slices). (C) A similarity index matrix compares each vector with all others along time: a patchy appearance shows that similar vectors were in charge of activity. (D) Dimensionality reduction using locally linear embedding (LLE) shows neuronal vectors projected in a two dimensional space with no units. Similar vectors grouped together (denoted by different colors) give raise to network states. The transitions among network states are denoted by arrows. Percentages give the probability to leave a given state. Colored dots and arrows represent the sequential activity of the circuit, that is, pools of neurons synchronized their firing and pass their activity from one pool of neurons to the other: cell assembly dynamics (Carrillo-Reid et al., 2008). Note reverberant trajectories in the sequence. Here and in the next figures, epochs (times of continuous image series) are separated by vertical dashed lines.

Mentions: Figure 1A illustrates a raster plot or matrix showing the activity of >100 neurons in a field of view within a striatal slice in control conditions. Each row in the plot represents the electrical activity of one neuron across a series of images (columns) recorded by means of calcium-imaging using fluo-8 (see Materials and Methods). Leftmost frame shows 3 min of activity (an epoch) in control striatal tissue without NMDA: note the scarcity of spontaneous activity and the absence of significant peaks of synchronization. In the next three frames (3 epochs 3 min each) it is shown an increase in activity involving dozens of striatal individual neurons (single cell resolution) after adding 2 μM NMDA into the bath saline. All three epochs display the NMDA-induced activity. Colored dots denote neurons firing together and belonging to a pool of neurons. Different colors denote different neuron pools. The activity of these neurons is vectorized (column vectors). Note that neuronal vectors alternate their activity along time, that is, the network transits from one set of neurons to the other as indicated by different colors.


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)

Assembly dynamics in the control striatal circuitry after NMDA. (A) Raster plot showing the simultaneous activity of >100 neurons in a striatal slice using calcium-imaging. Each row in the matrix represents the activity of a single neuron across the series of images (columns). Left epoch shows 3 min of activity in control striatal tissue without NMDA. Note scarce activity and the absence of peaks of synchronization. In the next three epochs, separated by dashed vertical lines, 9 min of activity are shown after adding 2 μM NMDA into the bath saline (denoted by horizontal black line on top). Note that many more dots, some of them colored, populate the matrix. Colored dots denote the synchronized activity of several neurons in a given column or neighboring columns (a neuron pool is then represented as a column vector). Note that different neuron pools produce the circuit activity along time. (B) Activity histogram at bottom is the summed neuronal activity (multicellular activity) from the raster plot above column by column (frame by frame in a given movie). The dashed line shows the level of significance for the spontaneous peaks of synchronization denoted by colors (obtained by Monte Carlo simulations; statistically significant neuronal vectors; n = 6 slices). (C) A similarity index matrix compares each vector with all others along time: a patchy appearance shows that similar vectors were in charge of activity. (D) Dimensionality reduction using locally linear embedding (LLE) shows neuronal vectors projected in a two dimensional space with no units. Similar vectors grouped together (denoted by different colors) give raise to network states. The transitions among network states are denoted by arrows. Percentages give the probability to leave a given state. Colored dots and arrows represent the sequential activity of the circuit, that is, pools of neurons synchronized their firing and pass their activity from one pool of neurons to the other: cell assembly dynamics (Carrillo-Reid et al., 2008). Note reverberant trajectories in the sequence. Here and in the next figures, epochs (times of continuous image series) are separated by vertical dashed lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3818482&req=5

Figure 1: Assembly dynamics in the control striatal circuitry after NMDA. (A) Raster plot showing the simultaneous activity of >100 neurons in a striatal slice using calcium-imaging. Each row in the matrix represents the activity of a single neuron across the series of images (columns). Left epoch shows 3 min of activity in control striatal tissue without NMDA. Note scarce activity and the absence of peaks of synchronization. In the next three epochs, separated by dashed vertical lines, 9 min of activity are shown after adding 2 μM NMDA into the bath saline (denoted by horizontal black line on top). Note that many more dots, some of them colored, populate the matrix. Colored dots denote the synchronized activity of several neurons in a given column or neighboring columns (a neuron pool is then represented as a column vector). Note that different neuron pools produce the circuit activity along time. (B) Activity histogram at bottom is the summed neuronal activity (multicellular activity) from the raster plot above column by column (frame by frame in a given movie). The dashed line shows the level of significance for the spontaneous peaks of synchronization denoted by colors (obtained by Monte Carlo simulations; statistically significant neuronal vectors; n = 6 slices). (C) A similarity index matrix compares each vector with all others along time: a patchy appearance shows that similar vectors were in charge of activity. (D) Dimensionality reduction using locally linear embedding (LLE) shows neuronal vectors projected in a two dimensional space with no units. Similar vectors grouped together (denoted by different colors) give raise to network states. The transitions among network states are denoted by arrows. Percentages give the probability to leave a given state. Colored dots and arrows represent the sequential activity of the circuit, that is, pools of neurons synchronized their firing and pass their activity from one pool of neurons to the other: cell assembly dynamics (Carrillo-Reid et al., 2008). Note reverberant trajectories in the sequence. Here and in the next figures, epochs (times of continuous image series) are separated by vertical dashed lines.
Mentions: Figure 1A illustrates a raster plot or matrix showing the activity of >100 neurons in a field of view within a striatal slice in control conditions. Each row in the plot represents the electrical activity of one neuron across a series of images (columns) recorded by means of calcium-imaging using fluo-8 (see Materials and Methods). Leftmost frame shows 3 min of activity (an epoch) in control striatal tissue without NMDA: note the scarcity of spontaneous activity and the absence of significant peaks of synchronization. In the next three frames (3 epochs 3 min each) it is shown an increase in activity involving dozens of striatal individual neurons (single cell resolution) after adding 2 μM NMDA into the bath saline. All three epochs display the NMDA-induced activity. Colored dots denote neurons firing together and belonging to a pool of neurons. Different colors denote different neuron pools. The activity of these neurons is vectorized (column vectors). Note that neuronal vectors alternate their activity along time, that is, the network transits from one set of neurons to the other as indicated by different colors.

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