Inhibition of Conditioned Stimulus Pathway Phosphoprotein 24 Expression Blocks the Reduction in A-Type Transient K⁺Current Produced by One-TrialIn VitroConditioning ofHermissenda

Abstract

Long-term intrinsic enhanced excitability is a characteristic of cellular plasticity and learning-dependent modifications in the activity of neural networks. The regulation of voltage-dependent K ϩ channels by phosphorylation/dephosphorylation and their localization is proposed to be important in the control of cellular plasticity. One-trial conditioning in Hermissenda results in enhanced excitability in sensory neurons, type B photoreceptors, of the conditioned stimulus pathway. Conditioning also regulates the phosphorylation of conditioned stimulus pathway phosphoprotein 24 (Csp24), a cytoskeletal-related protein containing multiple ␤-thymosin-like domains. Recently, it was shown that the downregulation of Csp24 expression mediated by an antisense oligonucleotide blocked the development of enhanced excitability in identified type B photoreceptors after one-trial conditioning without affecting short-term excitability. Here, we show using whole-cell patch recordings that one-trial in vitro conditioning applied to isolated photoreceptors produces a significant reduction in the amplitude of the A-type transient K ϩ current (I A ) detected 1.5-16 h after conditioning. One-trial conditioning produced a depolarized shift in the steady-state activation curve of I A without altering the inactivation curve. The conditioning-dependent reduction in I A was blocked by preincubation of the photoreceptors with Csp antisense oligonucleotide. These results provide an important link between Csp24, a cytoskeletal protein, and regulation of voltage-gated ion channels associated with intrinsic enhanced excitability underlying pavlovian conditioning.

Fear Conditioning and Extinction Differentially Modify the Intrinsic Excitability of Infralimbic Neurons

“…Neuronal excitability can be enhanced by closing large-conductance Ca 2 -activated K potassium channels (Shao et al, 1999;Traub et al, 2003;Brenner et al, 2005) or A-type potassium channels (Perez et al, 2006;Takeda et al, 2006;Wang and Schreurs, 2006), both of which are expressed in cortical neurons (Jin et al, 2000;Dong and White, 2003) and have been linked to increased bursting (Magee and Carruth, 1999;Jin et al, 2000;Traub et al, 2003;Gu et al, 2007). Interestingly, a decrease in A-type currents has been correlated with invertebrate learning (Yamoah et al, 2005) and hippocampal long-term potentiation (Frick et al, 2004). Additional experiments are underway to determine whether A-type or other potassium currents are reduced after extinction training.…”

Downregulation of thymosin β4 in neural progenitor grafts promotes spinal cord regeneration

“…This result confirms that actin-binding proteins are able to affect the distribution of ion channels and regulate receptor trafficking in neurons. (Redell et al, 2007;Yamoah et al, 2005). Moreover, the role of the actin network in regulating the localization of ion channels is important in establishing the electrical properties of neurons (Hattan et al, 2002;Petrecca et al, 2000).…”

Proteomic analysis of short- and intermediate-term memory in Hermissenda

“…Previous work has shown that Csp24 is phosphorylated by one-trial in vitro conditioning and multi-trial Pavlovian conditioning (Crow et al 1999, 2003; Crow and Xue-Bian 2000, 2003, 2007, 2010; Redell et al 2007). The depolarized shift in the activation curve of I A proposed to contribute to one-trial conditioning-dependent enhanced excitability is blocked by preincubation of sensory neurons with Csp antisense oligonucleotide (Yamoah et al 2005). …”

“…One-trial in vitro conditioning consists of pairing the CS (Light) with the application of 5-HT to the isolated nervous system. In vitro conditioning has been shown to produce multiple stages of time-dependent enhanced excitability in sensory neurons (photoreceptors), synaptic facilitation of the monosynaptic connection between sensory neurons and interneurons, and changes in protein phosphorylation (Crow & Forrester 1991,1993; Crow & Siddiqi 1997; Crow & Xue-Bian 2000, 2002, 2007, 2010; Crow et al 1996,1997,1998,1999, 2003; Yamoah et al 2005; Redell et al 2007). …”