View source for Aplysia R15 neuron

== 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 <i>parabolic burster</i> (Strumwasser, 1968) due to parabolic rise and fall of the interspike interval over the time-course of the burst.

[[Image:parabolicBurster.png|thumb|Parabolic bursting of R15. Unpublished data from RJB.]]

The mechanism of bursting in neuron R15 received extensive study in the 1970s and 1980s.  These works are reviewed quite comprehensively 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:

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

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 concentrations of Na<sup>+</sup> or Ca<sup>2+</sup> 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 account for the termination of the burst.  Ideally, this would involve the progressive inactivation of the negative-slope-region (NSR) current responsible for the initiation 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<sup>+</sup> current (Junge and Stephens, 1973), voltage-activation and Ca<sup>2+</sup>-inactivation of the NSR current (Adams and Levitan, 1985; Kramer and Zucker, 1985), 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, exactly how the neuron bursts has never been conclusively resolved.  Research on R15's ionic mechanisms largely stopped in the late 1980s.  Furthermore, subthreshold currents are difficult to quantify due to their low amplitude compared to other ionic currents in the cell membrane.