# Mechanisms for multiple activity modes of VTA dopamine neurons

## TL;DR

This paper explores how dopamine neurons in the VTA can switch between different firing modes and how this affects dopamine release.

## Contribution

The study introduces a computational model that explains multiple firing modes in VTA dopamine neurons based on SK conductance, drive, and GABA inhibition.

## Key findings

- Low SK conductance in neurons correlates with fast firing and burst activity requiring higher current for depolarization block.
- Strong GABA inhibition suppresses burst firing in dopamine neurons.
- Burst patterns terminating via depolarization block resemble in vivo observations under apamin application.

## Abstract

Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.