Myomodulin modulation of the Retzius cell and its role in the leech associative learning

Yong Wang, Purdue University

Abstract

Associative learning is a fundamental process in animals. The CS's ability to predict the US is key for the acquisition of an association. Consistent CS prediction of a US prevents functional “drop-out” of a critical component of one US pathway in the leech, the Retzius (R) cell. Throughout training predicted USs consistently cause an R cell to fire barrages of action potentials. In contrast, unpredicted USs initially elicit action potentials in the R cell, but gradually the R cell stops responding to the US. No learning occurs during unpredicted CS-US presentations. R cell firing releases serotonin (5-HT) which in turn exerts an inhibitory effect on the R cell through autoreceptors by opening Cl− channels and inducing a hyperpolariztion of R cell membrane potential. When a CS is activated prior to a US or a CS is applied prior to treatment of 5-HT, the normal 5-HT induced hyperpolarization in R cell is not observed. When myomodulin, a newly discovered neuropeptide, is perfused onto the R cell prior to the application of 5-HT, the normal effect of 5-HT is not observed. More intriguingly, pretreatment with myomodulin can prevent the R cell firing from undergoing “drop-out” during simultaneous behavioral and cellular recordings. Thus myomodulin modulation of the R cell appears to play an important role during animal associative learning. Using a combination of RP-HPLC and radioimmunoassay, a leech version of myomodulin peptide was purified from the leech CNS. Furthermore, a myomodulinergic synapse in the CNS of the animal, the S to R cell synapse, has been identified. This synapse has the hallmark properties of a typical peptidergic synapse. The S cells are monosynaptically activated by touch sensory neurons (T cells) during CS presentation. Therefore this synapse may be critical in the leech associative learning. Equally important is the mechanism by which myomodulin exerts its effects on the R cell. A systematic characterization of the currents modulated by myomodulin was carried out in this study. The significant findings are: (1) Myomodulin increases the excitability of the Retzius cell such that the cell fires more action potentials and shortens the latency to the first action potential in response to a step current pulse. (2) Myomodulin induces a novel Na+-mediated inward current near the cell resting membrane potential, which can readily account for the immediate small depolarization observed after myomodulin application when cells are monitored in current-clamp mode. (3) Myomodulin differentially modulates the two components of the K + currents IA and I K. Myomodulin has little or no effect on the fast activate-inactivate IA current, but greatly reduces the delayed rectifying IK current. (4) myomodulin decreases the voltage-gated Ca2+ current. By understanding the mechanism of myomodulin modulation of the R cell, we are now in a position to analyze the role of the R cell in a variety of leech behaviors and the plasticity of those behaviors.

Degree

Ph.D.

Advisors

Sahley, Purdue University.

Subject Area

Neurology

COinS