Computational Studies of the Role of Serotonin in the Basal Ganglia
It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson’s disease (PD), the serotonergic projections from the dorsal raphe nucleus release dopamine as a false transmitter, and there are strong indications that thi...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Janet eBest [verfasserIn] Michael C. Reed [verfasserIn] H. Frederik Nijhout [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2013 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Frontiers in Integrative Neuroscience - Frontiers Media S.A., 2008, 7(2013) |
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| Übergeordnetes Werk: |
volume:7 ; year:2013 |
| Links: |
|---|
| DOI / URN: |
10.3389/fnint.2013.00041 |
|---|
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| 520 | |a It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson’s disease (PD), the serotonergic projections from the dorsal raphe nucleus release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the balance between the pathways to favor the indirect pathway. Originally, balance was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum stabilizes the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson’s disease progression (until late phase). There may be situations in which there are physiological reasons to unbalance the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task. | ||
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| 650 | 4 | |a Serotonin | |
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10.3389/fnint.2013.00041 doi (DE-627)DOAJ002597608 (DE-599)DOAJ69177dd1e9974493a87b2c2f545cbcb3 DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Janet eBest verfasserin aut Computational Studies of the Role of Serotonin in the Basal Ganglia 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson’s disease (PD), the serotonergic projections from the dorsal raphe nucleus release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the balance between the pathways to favor the indirect pathway. Originally, balance was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum stabilizes the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson’s disease progression (until late phase). There may be situations in which there are physiological reasons to unbalance the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task. Basal Ganglia Serotonin mathematical model action selection direct pathway Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Michael C. Reed verfasserin aut H. Frederik Nijhout verfasserin aut In Frontiers in Integrative Neuroscience Frontiers Media S.A., 2008 7(2013) (DE-627)579826406 (DE-600)2452962-X 16625145 nnns volume:7 year:2013 https://doi.org/10.3389/fnint.2013.00041 kostenfrei https://doaj.org/article/69177dd1e9974493a87b2c2f545cbcb3 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fnint.2013.00041/full kostenfrei https://doaj.org/toc/1662-5145 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2013 |
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10.3389/fnint.2013.00041 doi (DE-627)DOAJ002597608 (DE-599)DOAJ69177dd1e9974493a87b2c2f545cbcb3 DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Janet eBest verfasserin aut Computational Studies of the Role of Serotonin in the Basal Ganglia 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson’s disease (PD), the serotonergic projections from the dorsal raphe nucleus release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the balance between the pathways to favor the indirect pathway. Originally, balance was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum stabilizes the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson’s disease progression (until late phase). There may be situations in which there are physiological reasons to unbalance the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task. Basal Ganglia Serotonin mathematical model action selection direct pathway Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Michael C. Reed verfasserin aut H. Frederik Nijhout verfasserin aut In Frontiers in Integrative Neuroscience Frontiers Media S.A., 2008 7(2013) (DE-627)579826406 (DE-600)2452962-X 16625145 nnns volume:7 year:2013 https://doi.org/10.3389/fnint.2013.00041 kostenfrei https://doaj.org/article/69177dd1e9974493a87b2c2f545cbcb3 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fnint.2013.00041/full kostenfrei https://doaj.org/toc/1662-5145 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2013 |
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It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson’s disease (PD), the serotonergic projections from the dorsal raphe nucleus release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the balance between the pathways to favor the indirect pathway. Originally, balance was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum stabilizes the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson’s disease progression (until late phase). There may be situations in which there are physiological reasons to unbalance the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task. |
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It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson’s disease (PD), the serotonergic projections from the dorsal raphe nucleus release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the balance between the pathways to favor the indirect pathway. Originally, balance was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum stabilizes the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson’s disease progression (until late phase). There may be situations in which there are physiological reasons to unbalance the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task. |
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It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson’s disease (PD), the serotonergic projections from the dorsal raphe nucleus release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the balance between the pathways to favor the indirect pathway. Originally, balance was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum stabilizes the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson’s disease progression (until late phase). There may be situations in which there are physiological reasons to unbalance the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task. |
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