Inverse Relationship between Basal Pacemaker Neuron Activity and Aversive Long-Term Memory Formation in Lymnaea stagnalis.

Nancy Dong,Zhong-Ping Feng

doi:10.3389/fncel.2016.00297

Abstract

Learning and memory formation are essential physiological functions. While quiescent neurons have long been the focus of investigations into the mechanisms of memory formation, there is increasing evidence that spontaneously active neurons also play key roles in this process and possess distinct rules of activity-dependent plasticity. In this study, we used a well-defined aversive learning model of aerial respiration in the mollusk Lymnaea stagnalis (L. stagnalis) to study the role of basal firing activity of the respiratory pacemaker neuron Right Pedal Dorsal 1 (RPeD1) as a determinant of aversive long-term memory (LTM) formation. We investigated the relationship between basal aerial respiration behavior and RPeD1 firing activity, and examined aversive LTM formation and neuronal plasticity in animals exhibiting different basal aerial respiration behavior. We report that animals with higher basal aerial respiration behavior exhibited early responses to operant conditioning and better aversive LTM formation. Early behavioral response to the conditioning procedure was associated with biphasic enhancements in the membrane potential, spontaneous firing activity and gain of firing response, with an early phase spanning the first 2 h after conditioning and a late phase that is observed at 24 h. Taken together, we provide the first evidence suggesting that lower neuronal activity at the time of learning may be correlated with better memory formation in spontaneously active neurons. Our findings provide new insights into the diversity of cellular rules of plasticity underlying memory formation.

Highlights

Learning and memory are essential abilities required for the survival of organisms
In order to examine the relationship between basal Right Pedal Dorsal 1 (RPeD1) firing activity and aversive long-term memory (LTM) formation ability, we first sought to separate animals that, despite undergoing the same conditioning paradigm, did and did not form LTM
Whereas animals labeled as ‘‘no-LTM’’ exhibited no significant changes in the total duration (P < 0.05) and frequency (P < 0.05) of pneumostome openings after conditioning, both parameters of the aerial respiration behavior were significantly reduced in animals labeled as ‘‘LTM’’

Summary

Introduction

Learning and memory are essential abilities required for the survival of organisms. The cellular and molecular mechanisms of memory formation have been largely focused on excitationdriven paradigms in quiescent neurons, which do not fire action potentials at rest. Instead of excitation, synaptic inhibition is found to be a common trigger for neural plasticity in spontaneously active neurons in the cerebellum (Nelson et al, 2003, 2005; Pugh and Raman, 2008, 2009; Hull et al, 2013) and striatum (Rueda-Orozco et al, 2009) in motor learning and the ventral tegmentum area, and subthalamic nucleus in reward- and drug-related learning (Mure et al, 2012; Creed et al, 2014; Ranaldi, 2014; Weiss et al, 2014). Synaptic plasticity is triggered by the post-inhibitory rebound depolarization following synaptic inhibition from Purkinje neurons (Pugh and Raman, 2006, 2008). Taken together, these findings indicate that spontaneously active neurons likely have distinct rules of information storage and transfer that warrant further study. Elucidating the similarities and differences in the rules of plasticity between spontaneously active and quiescent neurons will expand our understanding of the full complement of activity-induced plasticity mechanisms in the nervous system

Results

Discussion

Conclusion