AA/12-lipoxygenase signaling contributes to inhibitory learning in Hermissenda Type B photoreceptors

Walker Walker

doi:10.3389/fnbeh.2010.00050

Abstract

Conditioned inhibition (CI) is a major category of associative learning that occurs when an organism learns that one stimulus predicts the absence of another. In addition to being important in its own right, CI is interesting because its occurrence implies that the organism has formed an association between stimuli that are non-coincident. In contrast to other categories of associative learning that are dependent upon temporal contiguity (pairings) of stimuli, the neurobiology of CI is virtually unexplored. We have previously described a simple form of CI learning in Hermissenda, whereby animals’ phototactic behavior is increased by repeated exposures to explicitly unpaired (EU) presentations of light and rotation. EU conditioning also produces characteristic reductions in the excitability and light response, and increases several somatic K+ currents in Type B photoreceptors. Type B photoreceptors are a major site of plasticity for classical conditioning in Hermissenda. Because arachidonic acid (AA) and/or its metabolites open diverse K+ channels in many cell types, we examined the potential contribution of AA to CI. Our results indicate that AA contributes to one of the major effects of EU-conditioning on Type B photoreceptors: decreases in light-evoked spike activity. We find that AA increases the transient (IA) somatic K+ current in Type B photoreceptors, further mimicking CI training. In addition, our results indicate that metabolism of AA by a 12-lipoxygenase enzyme is critical for these effects of AA, and further that 12-lipoxygenase metabolites are apparently generated during CI training.

Highlights

An important, but poorly understood, issue in the cellular analysis of learning and memory is how the stimulus relationship of “non-coincidence” is encoded and represented within the brain
arachidonic acid (AA) and a 12-lipoxygenase metabolite reduced spike frequency in Type B photoreceptors, similar to the effects of explicitly unpaired (EU) conditioning We observed that application of AA to Type B photoreceptors of untrained Hermissenda resulted in a ∼20% reduction in spiking during the steady-state generator potentials (SSGP) photoresponse
Potential model for the involvement of AA in excitatory and inhibitory conditioning While we present evidence in this paper that AA indirectly mediates the reduction in spike frequency produced by EU training, AA has been reported to act synergistically with diacylglycerol (DAG) and Ca2+ to activate protein kinase C (PKC) in B cells (Lester et al, 1991), suggesting its involvement in excitatory conditioning (Talk et al, 1997; Muzzio et al, 2001).This potential dual role for AA signaling can be accommodated by several models

Summary

Introduction

But poorly understood, issue in the cellular analysis of learning and memory is how the stimulus relationship of “non-coincidence” is encoded and represented within the brain. Organisms learn that stimuli co-occur, as in standard forms of excitatory Pavlovian/classical conditioning (Domjan, 2010). If a different CS reliably predicts the absence of electric shock, the learning that results may be “safety signal” learning, or the conditioning of “relief ”, a central emotional state that is functionally opposite to that of fear. A common characterization of inhibitory Pavlovian/classical conditioning regards the organism as learning that one stimulus (the CS) predicts the absence of the other (the US) (Rescorla, 1969; Domjan, 2010), just as the organism learns that a CS predicts the presence of a US during excitatory conditioning

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