Responses of a bursting pacemaker to excitation reveal spatial segregation between bursting and spiking mechanisms

Abstract

Central pattern generators (CPGs) frequently include bursting neurons that serve as pacemakers for rhythm generation. Phase resetting curves (PRCs) can provide insight into mechanisms underlying phase locking in such circuits. PRCs were constructed for a pacemaker bursting complex in the pyloric circuit in the stomatogastric ganglion of the lobster and crab. This complex is comprised of the Anterior Burster (AB) neuron and two Pyloric Dilator (PD) neurons that are all electrically coupled. Artificial excitatory synaptic conductance pulses of different strengths and durations were injected into one of the AB or PD somata using the Dynamic Clamp. Previously, we characterized the inhibitory PRCs by assuming a single slow process that enabled synaptic inputs to trigger switches between an up state in which spiking occurs and a down state in which it does not. Excitation produced five different PRC shapes, which could not be explained with such a simple model. A separate dendritic compartment was required to separate the mechanism that generates the up and down phases of the bursting envelope (1) from synaptic inputs applied at the soma, (2) from axonal spike generation and (3) from a slow process with a slower time scale than burst generation. This study reveals that due to the nonlinear properties and compartmentalization of ionic channels, the response to excitation is more complex than inhibition.

Differential effects of conductances on the phase resetting curve of a bursting neuronal oscillator

“…Previous work has suggested that the H current has similar effects on the phase resetting curve as the leak current (Prinz et al 2003b); this was used as justification for not including the H current in the four-compartment model described in Maran et al (2011). Our results show that this is not the case; the H current and leak current have distinguishable effects on the PRC, and these effects are partly dependent on conductance location.…”

“…We suspected that the discrepancy between the effect of ḡ leak on PRCs in the model neuron database and its effect in the biological neuron partly arose from the fact that in the biological neuron, the locations of synaptic input, spike generation, and production of the voltage envelope are spatially separated. Injecting leak current solely into the soma may not adequately impact the mechanism that generates the slow-wave oscillation (Maran et al 2011) and therefore may have little effect on the PRC. Conversely, in the single-compartment model neuron, all phenomena effectively occur at a single point in space.…”

“…To do this, we utilized a four-compartment model from Maran et al (2011). Similar to previous neuron models (Soto-Trevino et al 2005b), this model used multiple compartments to separate the location of synaptic input (soma), the location of spike generation (axon), and the location of the mechanisms underlying the production of the voltage slow wave (lumped dendritic compartment).…”

“…We investigated whether the spatial separation of slow-wave generation, spike generation, and input location in the biological PD neuron played a role in producing the discrepancy between the database and dynamic clamp results by examining the four-compartment model. This model was developed with a goal of reproducing biological PRCs in the pacemaker kernel of the pyloric circuit and is thus suited to exploring the effects of conductance location and magnitude on inhibitory PRCs (Maran et al 2011). This model was previously used to demonstrate that the spatial separation of the mechanisms generating different aspects of the burst waveform (i.e.…”

“…To determine how the locations of specific ion channels influence their effect on the PRC, we modified a multi-compartment model described in Maran et al (2011). This model consists of four compartments that simulate: (1) the soma of one PD neuron, (2) a PD primary neurite, (3) a PD axon, and (4) the fine dendrites of both PDs and the AB neuron.…”