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Balanced plasticity and stability of the electrical properties of a molluscan modulatory interneuron after classical conditioning: a computational study.

Vavoulis DV, Nikitin ES, Kemenes I, Marra V, Feng J, Benjamin PR, Kemenes G - Front Behav Neurosci (2010)

Bottom Line: In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs.Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning.We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Warwick Coventry, UK.

ABSTRACT
The Cerebral Giant Cells (CGCs) are a pair of identified modulatory interneurons in the Central Nervous System of the pond snail Lymnaea stagnalis with an important role in the expression of both unconditioned and conditioned feeding behavior. Following single-trial food-reward classical conditioning, the membrane potential of the CGCs becomes persistently depolarized. This depolarization contributes to the conditioned response by facilitating sensory cell to command neuron synapses, which results in the activation of the feeding network by the conditioned stimulus. Despite the depolarization of the membrane potential, which enables the CGGs to play a key role in learning-induced network plasticity, there is no persistent change in the tonic firing rate or shape of the action potentials, allowing these neurons to retain their normal network function in feeding. In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs. We then used this model to elucidate how learning-induced changes in a somal persistent sodium and a delayed rectifier potassium current lead to a persistent depolarization of the CGCs whilst maintaining their firing rate. Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning. We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.

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Related in: MedlinePlus

Parameter estimation from voltage-clamp data. (A) Estimation of the steady-state activation of the persistent sodium current. Persistent sodium currents at equilibrium, I∞,NaP, were measured at the end of 800 ms-long voltage steps to membrane potentials in the range from −90 to +30 mV from a holding potential of −110 mV (Ai, open squares; Nikitin et al., 2006). The model for I∞,NaP (Eq. S11 in section Materials and Methods in Supplementary Material) was fitted against this data (Ai, solid line) permitting the estimation of the steady-state activation of the current, r∞, as a sigmoid function of the membrane potential (Aii). (B) Estimation of the steady-state activation and steady-state inactivation of the low-voltage-activated and high-voltage-activated calcium currents. The steady-state inactivation for ILVA, d∞, was computed by fitting a sigmoid curve to normalized peak currents recorded during voltage steps to −50 mV from holding membrane potentials between −100 mV and −30 mV (Bi, open squares; Staras et al., 2002). Similarly, for the steady-state inactivation of IHVA, f∞, we fitted a sigmoid curve to normalized peak currents recorded during voltage steps to 0 mV from holding membrane potentials between −60 mV and +15 mV (Bi, open circles; Staras et al., 2002). Subsequently, the model in Eq. S12 in Supplementary Material was fitted against the total calcium current induced during a voltage-ramp protocol changing the membrane potential from −100 mV to +30 mV over a time interval of 120 ms (Bii; Staras et al., 2002). The arrow in Bii indicates the low-voltage-activated component corresponding to ILVA. From the fitted model, we derived the steady-state activation for ILVA and IHVA (c∞ and e∞, respectively) as sigmoid functions of the membrane potential (Biii). (C) Estimation of the activation and inactivation kinetics for the transient (IA) and delayed-rectifier (ID) potassium currents. The model for the total potassium current under voltage-clamp (Eq. S13–S16 in Supplementary Material) was fitted to current traces induced during 100 ms-long voltage steps from a holding membrane potential of −90 mV to steps from −20 to +35 mV (Ci; Staras et al., 2002) using the full trace method (Willms et al., 1999). The arrow in Ci indicates the early transient component corresponding to IA. The fitted model permitted the estimation of the steady-state activation, a∞, and inactivation, b∞, for the transient potassium current IA, and the steady-state activation, n∞∗, for the delayed rectifier as illustrated in Cii. The corresponding relaxation times, τa, τb and , were also derived from the fitted model (Ciii). The estimated kinetic parameters for ID are marked with an asterisk, because they are further modified and receive their final values based on current clamp data.
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Figure 1: Parameter estimation from voltage-clamp data. (A) Estimation of the steady-state activation of the persistent sodium current. Persistent sodium currents at equilibrium, I∞,NaP, were measured at the end of 800 ms-long voltage steps to membrane potentials in the range from −90 to +30 mV from a holding potential of −110 mV (Ai, open squares; Nikitin et al., 2006). The model for I∞,NaP (Eq. S11 in section Materials and Methods in Supplementary Material) was fitted against this data (Ai, solid line) permitting the estimation of the steady-state activation of the current, r∞, as a sigmoid function of the membrane potential (Aii). (B) Estimation of the steady-state activation and steady-state inactivation of the low-voltage-activated and high-voltage-activated calcium currents. The steady-state inactivation for ILVA, d∞, was computed by fitting a sigmoid curve to normalized peak currents recorded during voltage steps to −50 mV from holding membrane potentials between −100 mV and −30 mV (Bi, open squares; Staras et al., 2002). Similarly, for the steady-state inactivation of IHVA, f∞, we fitted a sigmoid curve to normalized peak currents recorded during voltage steps to 0 mV from holding membrane potentials between −60 mV and +15 mV (Bi, open circles; Staras et al., 2002). Subsequently, the model in Eq. S12 in Supplementary Material was fitted against the total calcium current induced during a voltage-ramp protocol changing the membrane potential from −100 mV to +30 mV over a time interval of 120 ms (Bii; Staras et al., 2002). The arrow in Bii indicates the low-voltage-activated component corresponding to ILVA. From the fitted model, we derived the steady-state activation for ILVA and IHVA (c∞ and e∞, respectively) as sigmoid functions of the membrane potential (Biii). (C) Estimation of the activation and inactivation kinetics for the transient (IA) and delayed-rectifier (ID) potassium currents. The model for the total potassium current under voltage-clamp (Eq. S13–S16 in Supplementary Material) was fitted to current traces induced during 100 ms-long voltage steps from a holding membrane potential of −90 mV to steps from −20 to +35 mV (Ci; Staras et al., 2002) using the full trace method (Willms et al., 1999). The arrow in Ci indicates the early transient component corresponding to IA. The fitted model permitted the estimation of the steady-state activation, a∞, and inactivation, b∞, for the transient potassium current IA, and the steady-state activation, n∞∗, for the delayed rectifier as illustrated in Cii. The corresponding relaxation times, τa, τb and , were also derived from the fitted model (Ciii). The estimated kinetic parameters for ID are marked with an asterisk, because they are further modified and receive their final values based on current clamp data.

Mentions: Parameter estimation in the model from voltage-clamp data is summarized in Figure 1. Beginning with the persistent sodium current (INaP), we utilized information from current traces induced by 800 ms-long voltage steps to membrane potentials in the range from −90 to +30 mV from a holding potential of −110 mV (see Nikitin et al., 2006 for details of methods). The induced current persisted without significant inactivation for the duration of each step. The equilibrium current at the end of each step was modeled as a function of voltage (Eq. S11 in Materials and Methods in Supplementary Material) and it was fitted to the experimental data (Figure 1Ai). From the fitted model, the steady-state activation of the persistent-sodium current (r∞) was derived as a sigmoid function of the membrane potential (Figure 1Aii).


Balanced plasticity and stability of the electrical properties of a molluscan modulatory interneuron after classical conditioning: a computational study.

Vavoulis DV, Nikitin ES, Kemenes I, Marra V, Feng J, Benjamin PR, Kemenes G - Front Behav Neurosci (2010)

Parameter estimation from voltage-clamp data. (A) Estimation of the steady-state activation of the persistent sodium current. Persistent sodium currents at equilibrium, I∞,NaP, were measured at the end of 800 ms-long voltage steps to membrane potentials in the range from −90 to +30 mV from a holding potential of −110 mV (Ai, open squares; Nikitin et al., 2006). The model for I∞,NaP (Eq. S11 in section Materials and Methods in Supplementary Material) was fitted against this data (Ai, solid line) permitting the estimation of the steady-state activation of the current, r∞, as a sigmoid function of the membrane potential (Aii). (B) Estimation of the steady-state activation and steady-state inactivation of the low-voltage-activated and high-voltage-activated calcium currents. The steady-state inactivation for ILVA, d∞, was computed by fitting a sigmoid curve to normalized peak currents recorded during voltage steps to −50 mV from holding membrane potentials between −100 mV and −30 mV (Bi, open squares; Staras et al., 2002). Similarly, for the steady-state inactivation of IHVA, f∞, we fitted a sigmoid curve to normalized peak currents recorded during voltage steps to 0 mV from holding membrane potentials between −60 mV and +15 mV (Bi, open circles; Staras et al., 2002). Subsequently, the model in Eq. S12 in Supplementary Material was fitted against the total calcium current induced during a voltage-ramp protocol changing the membrane potential from −100 mV to +30 mV over a time interval of 120 ms (Bii; Staras et al., 2002). The arrow in Bii indicates the low-voltage-activated component corresponding to ILVA. From the fitted model, we derived the steady-state activation for ILVA and IHVA (c∞ and e∞, respectively) as sigmoid functions of the membrane potential (Biii). (C) Estimation of the activation and inactivation kinetics for the transient (IA) and delayed-rectifier (ID) potassium currents. The model for the total potassium current under voltage-clamp (Eq. S13–S16 in Supplementary Material) was fitted to current traces induced during 100 ms-long voltage steps from a holding membrane potential of −90 mV to steps from −20 to +35 mV (Ci; Staras et al., 2002) using the full trace method (Willms et al., 1999). The arrow in Ci indicates the early transient component corresponding to IA. The fitted model permitted the estimation of the steady-state activation, a∞, and inactivation, b∞, for the transient potassium current IA, and the steady-state activation, n∞∗, for the delayed rectifier as illustrated in Cii. The corresponding relaxation times, τa, τb and , were also derived from the fitted model (Ciii). The estimated kinetic parameters for ID are marked with an asterisk, because they are further modified and receive their final values based on current clamp data.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2871690&req=5

Figure 1: Parameter estimation from voltage-clamp data. (A) Estimation of the steady-state activation of the persistent sodium current. Persistent sodium currents at equilibrium, I∞,NaP, were measured at the end of 800 ms-long voltage steps to membrane potentials in the range from −90 to +30 mV from a holding potential of −110 mV (Ai, open squares; Nikitin et al., 2006). The model for I∞,NaP (Eq. S11 in section Materials and Methods in Supplementary Material) was fitted against this data (Ai, solid line) permitting the estimation of the steady-state activation of the current, r∞, as a sigmoid function of the membrane potential (Aii). (B) Estimation of the steady-state activation and steady-state inactivation of the low-voltage-activated and high-voltage-activated calcium currents. The steady-state inactivation for ILVA, d∞, was computed by fitting a sigmoid curve to normalized peak currents recorded during voltage steps to −50 mV from holding membrane potentials between −100 mV and −30 mV (Bi, open squares; Staras et al., 2002). Similarly, for the steady-state inactivation of IHVA, f∞, we fitted a sigmoid curve to normalized peak currents recorded during voltage steps to 0 mV from holding membrane potentials between −60 mV and +15 mV (Bi, open circles; Staras et al., 2002). Subsequently, the model in Eq. S12 in Supplementary Material was fitted against the total calcium current induced during a voltage-ramp protocol changing the membrane potential from −100 mV to +30 mV over a time interval of 120 ms (Bii; Staras et al., 2002). The arrow in Bii indicates the low-voltage-activated component corresponding to ILVA. From the fitted model, we derived the steady-state activation for ILVA and IHVA (c∞ and e∞, respectively) as sigmoid functions of the membrane potential (Biii). (C) Estimation of the activation and inactivation kinetics for the transient (IA) and delayed-rectifier (ID) potassium currents. The model for the total potassium current under voltage-clamp (Eq. S13–S16 in Supplementary Material) was fitted to current traces induced during 100 ms-long voltage steps from a holding membrane potential of −90 mV to steps from −20 to +35 mV (Ci; Staras et al., 2002) using the full trace method (Willms et al., 1999). The arrow in Ci indicates the early transient component corresponding to IA. The fitted model permitted the estimation of the steady-state activation, a∞, and inactivation, b∞, for the transient potassium current IA, and the steady-state activation, n∞∗, for the delayed rectifier as illustrated in Cii. The corresponding relaxation times, τa, τb and , were also derived from the fitted model (Ciii). The estimated kinetic parameters for ID are marked with an asterisk, because they are further modified and receive their final values based on current clamp data.
Mentions: Parameter estimation in the model from voltage-clamp data is summarized in Figure 1. Beginning with the persistent sodium current (INaP), we utilized information from current traces induced by 800 ms-long voltage steps to membrane potentials in the range from −90 to +30 mV from a holding potential of −110 mV (see Nikitin et al., 2006 for details of methods). The induced current persisted without significant inactivation for the duration of each step. The equilibrium current at the end of each step was modeled as a function of voltage (Eq. S11 in Materials and Methods in Supplementary Material) and it was fitted to the experimental data (Figure 1Ai). From the fitted model, the steady-state activation of the persistent-sodium current (r∞) was derived as a sigmoid function of the membrane potential (Figure 1Aii).

Bottom Line: In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs.Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning.We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Warwick Coventry, UK.

ABSTRACT
The Cerebral Giant Cells (CGCs) are a pair of identified modulatory interneurons in the Central Nervous System of the pond snail Lymnaea stagnalis with an important role in the expression of both unconditioned and conditioned feeding behavior. Following single-trial food-reward classical conditioning, the membrane potential of the CGCs becomes persistently depolarized. This depolarization contributes to the conditioned response by facilitating sensory cell to command neuron synapses, which results in the activation of the feeding network by the conditioned stimulus. Despite the depolarization of the membrane potential, which enables the CGGs to play a key role in learning-induced network plasticity, there is no persistent change in the tonic firing rate or shape of the action potentials, allowing these neurons to retain their normal network function in feeding. In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs. We then used this model to elucidate how learning-induced changes in a somal persistent sodium and a delayed rectifier potassium current lead to a persistent depolarization of the CGCs whilst maintaining their firing rate. Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning. We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.

No MeSH data available.


Related in: MedlinePlus