Apamin improves learning in an object recognition task in rats

Deschaux, Olivier; Bizot, Jean-Charles; Goyffon, M.

doi:10.1016/s0304-3940(97)13367-5

Cited by 81 publications

(55 citation statements)

References 13 publications

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“…Furthermore, there is evidence that application of apamin in vivo improves learning and memory retention in rats (40,41). Taken together with our results, these findings open a number of questions on the possible role of apamin-sensitive SK channels in modulating the integration of synaptic signals in hippocampal pyramidal neurons.…”

Section: Resultssupporting

confidence: 81%

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Stocker

Krause

Pedarzani

1999

Proc. Natl. Acad. Sci. U.S.A.

360

435

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In hippocampal and other cortical neurons, action potentials are followed by afterhyperpolarizations (AHPs) generated by the activation of small-conductance Ca 2؉ -activated K ؉ channels (SK channels). By shaping the neuronal firing pattern, these AHPs contribute to the regulation of excitability and to the encoding function of neurons. Here we report that CA1 pyramidal neurons express an AHP current that is suppressed by apamin and is involved in the control of repetitive firing. This current presents distinct kinetic and pharmacological features, and it is modulated differently than the apamin-insensitive slow AHP current. Furthermore, our in situ hybridizations show that the apaminsensitive SK subunits are expressed in CA1 pyramidal neurons, providing a potential molecular correlate to the apaminsensitive AHP current. Altogether, these results clarify the discrepancy between the reported high density of apaminbinding sites in the CA1 region and the apparent lack of an apamin-sensitive current in CA1 pyramidal neurons, and they may explain the effects of this toxin on hippocampal synaptic plasticity and learning.In many neurons of the central nervous system, action potentials are followed by a rise in intracellular Ca 2ϩ leading to a prolonged afterhyperpolarization (AHP) of the membrane (1-4). The currents underlying the AHP are mediated by small-conductance voltage-insensitive Ca 2ϩ -activated K ϩ channels (SK channels), and they can be classified into two groups on the basis of their kinetic and pharmacological properties (5): (i) I AHP is sensitive to the bee venom toxin apamin and presents a relatively fast activation and decay (6); (ii) sI AHP (where s stands for slow) is apamin insensitive, rises to peak and decays with time constants of several hundreds of milliseconds, and is modulated by many neurotransmitters (1, 4). Functionally, activation of I AHP controls the firing frequency in tonically spiking neurons, whereas activation of sI AHP leads to spike frequency adaptation (5). While most excitable cells present an apamin-sensitive I AHP , only a few nerve cells exhibit an apamin-insensitive sI AHP , or both types of currents (4, 5). In the hippocampus, electrophysiological experiments have so far shown a peculiar segregation of AHP currents in different types of neurons, with pyramidal neurons presenting exclusively sI AHP (1, 7), and oriens-alveus interneurons only I AHP (8). These results are in contrast with studies on the distribution of apamin-binding sites in rat brain sections, which show the highest density in the hippocampal CA1 region (9, 10).Three members of the SK family of K ϩ channels have recently been cloned (11). All of them are voltage-insensitive and activated by submicromolar intracellular Ca 2ϩ . Two of them, SK2 and SK3, are blocked by apamin, whereas SK1 is apamin insensitive (11). Given these features, the SK channel subunits cloned so far are likely to participate in the formation of native SK channels, giving rise to apamin-sensitive and -insensitive AHP currents i...

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Section: Resultssupporting

confidence: 81%

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Stocker

Krause

Pedarzani

1999

Proc. Natl. Acad. Sci. U.S.A.

360

435

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“…However, this claim is not substantiated by recent findings. Independent laboratories have demonstrated that in rats, apamin enhances the induction of synaptic plasticity (Behnisch and Reymann, 1998;Norris et al, 1998) and facilitates nonspatial memory (Deschaux et al, 1997;Fournier et al, 2001). Our data suggest that apamin exerts its influence on an early stage of memory encoding, an effect that may not have been detected given the approaches used previously.…”

Section: Discussionmentioning

confidence: 59%

Small Conductance Ca²⁺-Activated K⁺Channels Modulate Synaptic Plasticity and Memory Encoding

Stackman¹,

Hammond²,

Linardatos³

et al. 2002

J. Neurosci.

254

227

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Activity-dependent changes in neuronal excitability and synaptic strength are thought to underlie memory encoding. In hippocampal CA1 neurons, small conductance Ca 2ϩ -activated K ϩ (SK) channels contribute to the afterhyperpolarization, affecting neuronal excitability. In the present study, we examined the effect of apamin-sensitive SK channels on the induction of hippocampal synaptic plasticity in response to a range of stimulation frequencies. In addition, the role of apamin-sensitive SK channels on hippocampal-dependent memory encoding and retention was also tested. The results show that blocking SK channels with apamin increased the excitability of hippocampal neurons and facilitated the induction of synaptic plasticity by shifting the modification threshold to lower frequencies. This facilitation was NMDA receptor (NMDAR) dependent and appeared to be postsynaptic. Mice treated with apamin demonstrated accelerated hippocampal-dependent spatial and nonspatial memory encoding. They required fewer trials to learn the location of a hidden platform in the Morris water maze and less time to encode object memory in an object-recognition task compared with saline-treated mice. Apamin did not influence long-term retention of spatial or nonspatial memory. These data support a role for SK channels in the modulation of hippocampal synaptic plasticity and hippocampal-dependent memory encoding.

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“…Activation of these potassium channels effectively shunts the postsynaptic membrane and reduces the amplitude of excitatory synaptic potentials (Faber et al, 2005;Ngo-Anh et al, 2005;Bloodgood and Sabatini, 2007). Thus, blockade of SK channels with specific inhibitors, such as apamin, enhances synaptic transmission and likely underlies the effects of apamin on learning (Deschaux et al, 1997;Stackman et al, 2002). In this study, we have shown that in lateral amygdala pyramidal neurons postsynaptic SK channels require the actin cytoskeleton for their stability, being endocytosed constitutively by a dynamindependent mechanism, with new channels transported back to the synapse via the actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Modulation of SK Channel Trafficking by Beta Adrenoceptors Enhances Excitatory Synaptic Transmission and Plasticity in the Amygdala

Faber

Delaney

Power³

et al. 2008

J. Neurosci.

101

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Emotionally arousing events are particularly well remembered. This effect is known to result from the release of stress hormones and activation of ␤ adrenoceptors in the amygdala. However, the underlying cellular mechanisms are not understood. Small conductance calcium-activated potassium (SK) channels are present at glutamatergic synapses where they limit synaptic transmission and plasticity. Here, we show that ␤ adrenoceptor activation regulates synaptic SK channels in lateral amygdala pyramidal neurons, through activation of protein kinase A. We show that SK channels are constitutively recycled from the postsynaptic membrane and that activation of ␤ adrenoceptors removes SK channels from excitatory synapses. This results in enhanced synaptic transmission and plasticity. Our findings demonstrate a novel mechanism by which ␤ adrenoceptors control synaptic transmission and plasticity, through regulation of SK channel trafficking, and suggest that modulation of synaptic SK channels may contribute to ␤ adrenoceptor-mediated potentiation of emotional memories.

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Apamin improves learning in an object recognition task in rats

Cited by 81 publications

References 13 publications

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Small Conductance Ca²⁺-Activated K⁺Channels Modulate Synaptic Plasticity and Memory Encoding

Modulation of SK Channel Trafficking by Beta Adrenoceptors Enhances Excitatory Synaptic Transmission and Plasticity in the Amygdala

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Apamin improves learning in an object recognition task in rats

Cited by 81 publications

References 13 publications

An apamin-sensitive Ca 2+ -activated K + current in hippocampal pyramidal neurons

An apamin-sensitive Ca 2+ -activated K + current in hippocampal pyramidal neurons

Small Conductance Ca2+-Activated K+Channels Modulate Synaptic Plasticity and Memory Encoding

Modulation of SK Channel Trafficking by Beta Adrenoceptors Enhances Excitatory Synaptic Transmission and Plasticity in the Amygdala

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An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

An apamin-sensitive Ca ²⁺ -activated K ⁺ current in hippocampal pyramidal neurons

Small Conductance Ca²⁺-Activated K⁺Channels Modulate Synaptic Plasticity and Memory Encoding