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Regulation and functional roles of rebound potentiation at cerebellar stellate cell-Purkinje cell synapses.

Hirano T, Kawaguchi SY - Front Cell Neurosci (2014)

Bottom Line: RP induction depends on binding of GABAAR with GABAAR associated protein (GABARAP) which is regulated by Ca(2+)/calmodulin-dependent kinase II (CaMKII).Recent studies have revealed that the subunit composition of CaMKII has significant impact on RP induction.Thus, RP is involved in a certain type of motor learning.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, Graduate School of Science, Kyoto University Kitashirakawa-Oiwake-cho Kyoto, Japan.

ABSTRACT
Purkinje cells receive both excitatory and inhibitory synaptic inputs and send sole output from the cerebellar cortex. Long-term depression (LTD), a type of synaptic plasticity, at excitatory parallel fiber-Purkinje cell synapses has been studied extensively as a primary cellular mechanism of motor learning. On the other hand, at inhibitory synapses on a Purkinje cell, postsynaptic depolarization induces long-lasting potentiation of GABAergic synaptic transmission. This synaptic plasticity is called rebound potentiation (RP), and its molecular regulatory mechanisms have been studied. The increase in intracellular Ca(2+) concentration caused by depolarization induces RP through enhancement of GABAA receptor (GABAAR) responsiveness. RP induction depends on binding of GABAAR with GABAAR associated protein (GABARAP) which is regulated by Ca(2+)/calmodulin-dependent kinase II (CaMKII). Whether RP is induced or not is determined by the balance between phosphorylation and de-phosphorylation activities regulated by intracellular Ca(2+) and by metabotropic GABA and glutamate receptors. Recent studies have revealed that the subunit composition of CaMKII has significant impact on RP induction. A Purkinje cell expresses both α- and β-CaMKII, and the latter has much higher affinity for Ca(2+)/calmodulin than the former. It was shown that when the relative amount of α- to β-CaMKII is large, RP induction is suppressed. The functional significance of RP has also been studied using transgenic mice in which a peptide inhibiting association of GABARAP and GABAAR is expressed selectively in Purkinje cells. The transgenic mice show abrogation of RP and subnormal adaptation of vestibulo-ocular reflex (VOR), a type of motor learning. Thus, RP is involved in a certain type of motor learning.

No MeSH data available.


Related in: MedlinePlus

Vestibulo-ocular reflex (VOR) and its adaptation. VOR is induced by rotating a turntable on which a mouse is fixed in the dark. In VOR eyeballs turn in the opposite direction of head turn. VOR undergoes adaptive modifications. When a wild-type mouse and a surrounding screen with vertical black and white stripes are rotated in opposite directions in the light (VOR-up training), the gain of VOR increases gradually. In contrast, when the rotations are in the same direction (VOR-down training), the gain decreases.
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Figure 4: Vestibulo-ocular reflex (VOR) and its adaptation. VOR is induced by rotating a turntable on which a mouse is fixed in the dark. In VOR eyeballs turn in the opposite direction of head turn. VOR undergoes adaptive modifications. When a wild-type mouse and a surrounding screen with vertical black and white stripes are rotated in opposite directions in the light (VOR-up training), the gain of VOR increases gradually. In contrast, when the rotations are in the same direction (VOR-down training), the gain decreases.

Mentions: Then, we evaluated the motor control and learning ability of the transgenic mice by examining reflex eye movement, vestibulo-ocular reflex (VOR; Figure 4). VOR is a reflex to turn an eyeball in the opposite direction of head turn, and works to stabilize visual image during head motion (Robinson, 1981). VOR undergoes adaptive modification in the direction to reduce image slip on a retina, which has been regarded as a model paradigm of cerebellum-dependent motor learning (Ito, 1982, 2011; Nagao, 1989; Lisberger et al., 1994; du Lac et al., 1995; Hirata and Highstein, 2001; Katoh et al., 2005; Hirano, 2013a). In experiments, a mouse is rotated sinusoidally on a rotating table, and a surrounding external screen with vertical black and white stripes is also rotated simultaneously (Tanaka et al., 2013). When the screen rotation is in the opposite direction to mouse rotation, the gain of VOR increases gradually in a wild-type mouse, and when the rotation is in the same direction, the gain decreases. These changes of VOR in a wild-type mouse are in the direction to reduce image motion on a retina and adaptive (Figure 4). These adaptive modifications of VOR amplitudes are suppressed in the transgenic mice defective in RP. Thus, transgenic mice defective in RP show defects in a type of motor learning, indicating that RP contributes to motor learning. However, it should be noted that these results do not rule out a possible contribution of LTD or other plasticity to motor learning. Indeed, adaptation of optokinetic response, another type of reflex eye movement, and reduced VOR adaptation occur in the RP-deficient mice (Tanaka et al., 2013). Considering similarities in induction conditions (Kawaguchi and Hirano, 2013) and suppressive effects on Purkinje cell activity between RP and LTD, they might synergistically support motor learning.


Regulation and functional roles of rebound potentiation at cerebellar stellate cell-Purkinje cell synapses.

Hirano T, Kawaguchi SY - Front Cell Neurosci (2014)

Vestibulo-ocular reflex (VOR) and its adaptation. VOR is induced by rotating a turntable on which a mouse is fixed in the dark. In VOR eyeballs turn in the opposite direction of head turn. VOR undergoes adaptive modifications. When a wild-type mouse and a surrounding screen with vertical black and white stripes are rotated in opposite directions in the light (VOR-up training), the gain of VOR increases gradually. In contrast, when the rotations are in the same direction (VOR-down training), the gain decreases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927423&req=5

Figure 4: Vestibulo-ocular reflex (VOR) and its adaptation. VOR is induced by rotating a turntable on which a mouse is fixed in the dark. In VOR eyeballs turn in the opposite direction of head turn. VOR undergoes adaptive modifications. When a wild-type mouse and a surrounding screen with vertical black and white stripes are rotated in opposite directions in the light (VOR-up training), the gain of VOR increases gradually. In contrast, when the rotations are in the same direction (VOR-down training), the gain decreases.
Mentions: Then, we evaluated the motor control and learning ability of the transgenic mice by examining reflex eye movement, vestibulo-ocular reflex (VOR; Figure 4). VOR is a reflex to turn an eyeball in the opposite direction of head turn, and works to stabilize visual image during head motion (Robinson, 1981). VOR undergoes adaptive modification in the direction to reduce image slip on a retina, which has been regarded as a model paradigm of cerebellum-dependent motor learning (Ito, 1982, 2011; Nagao, 1989; Lisberger et al., 1994; du Lac et al., 1995; Hirata and Highstein, 2001; Katoh et al., 2005; Hirano, 2013a). In experiments, a mouse is rotated sinusoidally on a rotating table, and a surrounding external screen with vertical black and white stripes is also rotated simultaneously (Tanaka et al., 2013). When the screen rotation is in the opposite direction to mouse rotation, the gain of VOR increases gradually in a wild-type mouse, and when the rotation is in the same direction, the gain decreases. These changes of VOR in a wild-type mouse are in the direction to reduce image motion on a retina and adaptive (Figure 4). These adaptive modifications of VOR amplitudes are suppressed in the transgenic mice defective in RP. Thus, transgenic mice defective in RP show defects in a type of motor learning, indicating that RP contributes to motor learning. However, it should be noted that these results do not rule out a possible contribution of LTD or other plasticity to motor learning. Indeed, adaptation of optokinetic response, another type of reflex eye movement, and reduced VOR adaptation occur in the RP-deficient mice (Tanaka et al., 2013). Considering similarities in induction conditions (Kawaguchi and Hirano, 2013) and suppressive effects on Purkinje cell activity between RP and LTD, they might synergistically support motor learning.

Bottom Line: RP induction depends on binding of GABAAR with GABAAR associated protein (GABARAP) which is regulated by Ca(2+)/calmodulin-dependent kinase II (CaMKII).Recent studies have revealed that the subunit composition of CaMKII has significant impact on RP induction.Thus, RP is involved in a certain type of motor learning.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, Graduate School of Science, Kyoto University Kitashirakawa-Oiwake-cho Kyoto, Japan.

ABSTRACT
Purkinje cells receive both excitatory and inhibitory synaptic inputs and send sole output from the cerebellar cortex. Long-term depression (LTD), a type of synaptic plasticity, at excitatory parallel fiber-Purkinje cell synapses has been studied extensively as a primary cellular mechanism of motor learning. On the other hand, at inhibitory synapses on a Purkinje cell, postsynaptic depolarization induces long-lasting potentiation of GABAergic synaptic transmission. This synaptic plasticity is called rebound potentiation (RP), and its molecular regulatory mechanisms have been studied. The increase in intracellular Ca(2+) concentration caused by depolarization induces RP through enhancement of GABAA receptor (GABAAR) responsiveness. RP induction depends on binding of GABAAR with GABAAR associated protein (GABARAP) which is regulated by Ca(2+)/calmodulin-dependent kinase II (CaMKII). Whether RP is induced or not is determined by the balance between phosphorylation and de-phosphorylation activities regulated by intracellular Ca(2+) and by metabotropic GABA and glutamate receptors. Recent studies have revealed that the subunit composition of CaMKII has significant impact on RP induction. A Purkinje cell expresses both α- and β-CaMKII, and the latter has much higher affinity for Ca(2+)/calmodulin than the former. It was shown that when the relative amount of α- to β-CaMKII is large, RP induction is suppressed. The functional significance of RP has also been studied using transgenic mice in which a peptide inhibiting association of GABARAP and GABAAR is expressed selectively in Purkinje cells. The transgenic mice show abrogation of RP and subnormal adaptation of vestibulo-ocular reflex (VOR), a type of motor learning. Thus, RP is involved in a certain type of motor learning.

No MeSH data available.


Related in: MedlinePlus