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Event timing in associative learning: from biochemical reaction dynamics to behavioural observations.

Yarali A, Nehrkorn J, Tanimoto H, Herz AV - PLoS ONE (2012)

Bottom Line: During training, an odour-induced Ca(++) signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca(++)-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour.Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning.We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute of Neurobiology, Martinsried, Germany. yarali@neuro.mpg.de

ABSTRACT
Associative learning relies on event timing. Fruit flies for example, once trained with an odour that precedes electric shock, subsequently avoid this odour (punishment learning); if, on the other hand the odour follows the shock during training, it is approached later on (relief learning). During training, an odour-induced Ca(++) signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca(++)-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour. In Aplysia, the effect of serotonin on the corresponding adenylate cyclase is bi-directionally modulated by Ca(++), depending on the relative timing of the two inputs. Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning. We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems.

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Related in: MedlinePlus

An alternative model for adenlyate cyclase regulation by the transmitter.To complement our main analysis based on the model adapted from [46] and shown in Fig. 3A, we finally use a simpler model variant [45]. Here, the transmitter reversibly binds to its respective G protein coupled receptor (GPCR) to form an active complex (Transmitter/GPCR*). This complex then dissociates, or it interacts with the G protein (G) to activate it (G*). The trimeric nature of the G protein is ignored (compare with Fig. 3A). G* on the one hand spontaneously deactivates (G), on the other hand it reversibly interacts with the adenylate cyclase (AC) to form an enzymatically active complex (G*/AC*), which serves as the system's output. The effect of Ca++ is implemented the same way as in Fig. 3A.
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pone-0032885-g009: An alternative model for adenlyate cyclase regulation by the transmitter.To complement our main analysis based on the model adapted from [46] and shown in Fig. 3A, we finally use a simpler model variant [45]. Here, the transmitter reversibly binds to its respective G protein coupled receptor (GPCR) to form an active complex (Transmitter/GPCR*). This complex then dissociates, or it interacts with the G protein (G) to activate it (G*). The trimeric nature of the G protein is ignored (compare with Fig. 3A). G* on the one hand spontaneously deactivates (G), on the other hand it reversibly interacts with the adenylate cyclase (AC) to form an enzymatically active complex (G*/AC*), which serves as the system's output. The effect of Ca++ is implemented the same way as in Fig. 3A.

Mentions: Finally, we test the generality of our results using an alternative model for the regulation of the adenylate cyclase by the transmitter [45]. This model (Fig. 9) includes only a single biochemical step for the GPCR activation and it ignores the trimeric nature of the G protein. In addition to its reduced complexity (i.e. five instead of nine differential equations), it differs from the first model (Fig. 3A) in terms of the initial concentrations of the molecules, as well as the reaction rate constants (see Materials and Methods for details).


Event timing in associative learning: from biochemical reaction dynamics to behavioural observations.

Yarali A, Nehrkorn J, Tanimoto H, Herz AV - PLoS ONE (2012)

An alternative model for adenlyate cyclase regulation by the transmitter.To complement our main analysis based on the model adapted from [46] and shown in Fig. 3A, we finally use a simpler model variant [45]. Here, the transmitter reversibly binds to its respective G protein coupled receptor (GPCR) to form an active complex (Transmitter/GPCR*). This complex then dissociates, or it interacts with the G protein (G) to activate it (G*). The trimeric nature of the G protein is ignored (compare with Fig. 3A). G* on the one hand spontaneously deactivates (G), on the other hand it reversibly interacts with the adenylate cyclase (AC) to form an enzymatically active complex (G*/AC*), which serves as the system's output. The effect of Ca++ is implemented the same way as in Fig. 3A.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316544&req=5

pone-0032885-g009: An alternative model for adenlyate cyclase regulation by the transmitter.To complement our main analysis based on the model adapted from [46] and shown in Fig. 3A, we finally use a simpler model variant [45]. Here, the transmitter reversibly binds to its respective G protein coupled receptor (GPCR) to form an active complex (Transmitter/GPCR*). This complex then dissociates, or it interacts with the G protein (G) to activate it (G*). The trimeric nature of the G protein is ignored (compare with Fig. 3A). G* on the one hand spontaneously deactivates (G), on the other hand it reversibly interacts with the adenylate cyclase (AC) to form an enzymatically active complex (G*/AC*), which serves as the system's output. The effect of Ca++ is implemented the same way as in Fig. 3A.
Mentions: Finally, we test the generality of our results using an alternative model for the regulation of the adenylate cyclase by the transmitter [45]. This model (Fig. 9) includes only a single biochemical step for the GPCR activation and it ignores the trimeric nature of the G protein. In addition to its reduced complexity (i.e. five instead of nine differential equations), it differs from the first model (Fig. 3A) in terms of the initial concentrations of the molecules, as well as the reaction rate constants (see Materials and Methods for details).

Bottom Line: During training, an odour-induced Ca(++) signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca(++)-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour.Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning.We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute of Neurobiology, Martinsried, Germany. yarali@neuro.mpg.de

ABSTRACT
Associative learning relies on event timing. Fruit flies for example, once trained with an odour that precedes electric shock, subsequently avoid this odour (punishment learning); if, on the other hand the odour follows the shock during training, it is approached later on (relief learning). During training, an odour-induced Ca(++) signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca(++)-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour. In Aplysia, the effect of serotonin on the corresponding adenylate cyclase is bi-directionally modulated by Ca(++), depending on the relative timing of the two inputs. Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning. We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems.

Show MeSH
Related in: MedlinePlus