Aplysia R15 neuron

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Author: Dr. Robert Butera, Georgia Tech, Atlanta, GA

1 Introduction
2 Electrophysiological Properties of Bursting
3 Neuromodulation of Bursting
4 Computational Models of R15 Burst Dynamics and Modulation
5 Physiological Function of R15

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Introduction

Neuron R15, located in the abdominal ganglion of the gastropod mollusc Aplysia Californica, is the first intrinsically bursting neuron to receive extensive study using single cell electrophysiology techniques. Much of the investigation of the nature of electrical bursting of single neurons was motivated by the initial study of this neuron, and it was later one of the first to receive extensive study of the role of neuromodulation in biasing single neuron burst dynamics.

Arvanitaki (1941) had recorded electrical activity extracellularly from various neuronal somata that were distinct and visually identifable. Soon thereafter, the technique of intracellular recording had been invented and was adopted as a tool for investigating the electrical dynamics of visually identifiable neurons in Aplysia. Arvanitaki and Chalazonitis (1955) and simultaneously Tauc (1954) published the first reports of a distinct visually identifiable neuron in the abdominal ganglion of Aplysia, now called R15 (Cogeshall et al., 1966; Frazier et al., 1967).

The study of R15 was accelerated when Eric Kandel adopted Aplysia as his animal model for studying the cellular basis of behavior. Kandel and his colleagues named many of the visually identifiable neurons in the ganglia of Aplysia and mapped out many of Aplysia's neuron circuits. Much of this work continues today.

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Electrophysiological Properties of Bursting

Early studies of R15 could find no evidence of rhythmic synaptic input or synchronous activity in connected neurons, leading to the conclusion that bursting in R15 was endogenous. It was shown that isolated somata could continue to burst after ligature (Alving, 1968) or isolated dissection (Chen et al., 1971). The bursting rhythm could also be phase-shifted by well-timed inputs to the soma (Pinsker, 1977), further supporting the idea that the rhythm was intrinsic to the neuron itself. R15 has been referred to as a parabolic burster (Strumwasser, 1968) due to parabolic rise and fall of the interspike interval over the time-course of the burst.

The mechanism of bursting in neuron R15 received extensive study in the 1970s and 1980s. These works are reviewed quite comprehensive in “The generation and modulation of endogenous rhythmicity in the Aplysia bursting pacemaker neurone R15” (Adams and Benson, 1985). In fact, very little experimental work on the ionic basis of bursting in R15 has been published since their comprehensive review article. Early investigators quickly identified several key features associated with the bursting rhythm, features that have now become recognized as common to many intrinsically bursting neurons. These features include:

the existence and importance of a "negative slope region" in the current-voltage (I-V) curve;
the recognition that the onset, offset, and progression of the burst were associated with ionic conductances that changed slowly during the burst; and
the role of an inward cationic current in initiating the burst

Nevertheless, the literature on this topic is a “chaos of conflicting observations and interpretations” (Adams and Benson, 1985). Some investigators found that a subthreshold oscillation persisted in the presence of tetrodotoxin (TTX), while others did not. Some investigators criticized many of the published studies, as they involved significant changes in the concentations of Na⁺ or Ca²⁺ which significantly altered membrane properties. One laboratory reported that "freshly opened" TTX blocked the subthreshold oscillations, but not if the vial of TTX had been opened for one day. What is agreed upon is that a cationic current is responsible for the negative slope region and the initiation of the burst.

A key point of dispute is the identification of an ionic mechanism that changes slowly during the burst and can accoun for the termination of the burst. Ideally, this would involve the progressive inactivation of the negative-slope-region (NSR) current responsible for the inititation of the burst or the slow activation of an outward current to counteract this current. Proposed mechanisms have included the slow activation and subsequent inactivation of an outward K⁺ current (NEED REF), voltage-activation and Ca²⁺-inactivation of the NSR current (REFS: Adams/Benson/Gage, Kramer Zucker), and a hyperpolarization activated current that summates throughout the burst (Adams, 1985).

While many models of bursting in R15 exist largely based on Adams and Benson's proposed model, these issues exactly how the neuron bursts have never been conclusively resolved. Research on R15's ionic mechanisms largely stopped in the late 1980s, and subthreshold currents are difficult to quantify due to their low amplitude compared to other ionic currents in the cell membrane.

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