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bioRxiv · 10.1101/053637

Dopamine neurons change the type of excitability in response to stimuli

Ekaterina Morozova·Denis Zakharov·Boris Gutkin·Christopher Lapish·Alexey Kuznetsov
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Abstract

The dynamics of neural excitability determine the neuronal response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance based biophysical model, and its regulation by intrinsic and synaptic currents. By calibrating the model to reproduce low frequency tonic firing, NMDA excitation is balanced by GABA-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency balanced state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized GABAR reversal potential or co-activation of AMPARs leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of NMDARs together with AMPARs and GABARs shifts the the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I excitability in dopamine neurons might be important for low firing rates and fine-tuning basal dopamine levels, while switching excitability to type II during NMDAR and AMPAR activation may facilitate a transient increase in dopamine concentration, as type II neurons are more amenable to synchronization.\n\nAuthor summaryDopamine neurons play a central role in guiding motivated behaviors. However, complete understanding of computations these neurons perform to encode rewarding and salient stimuli is still forthcoming. Network connectivity influences neural responses to stimuli but so do intrinsic excitability properties of individual neurons, as they define their synchronization properties and neural coding strategy. We investigated the excitability type of the DA neuron and found that, depending on the synaptic and intrinsic current composition, DA neurons can switch from type I to type II excitability. In short, without synaptic inputs or under balanced excitatory and inhibitory inputs DA neurons exhibits type I excitability, while excitatory AMPAR inputs can switch the neuron to type II. Type I neurons are best suited for coding the stimulus intensity due to their ability to smoothly decrease the firing rate. Type I excitability might be important for achieving low a basal DA concentration necessary for normal brain functioning. Switching to type II excitability further enables robust transient DA release of heterogeneous DA neuron population in response to correlated inputs, partially due to evoked population synchrony.

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Ekaterina Morozova, Denis Zakharov, Boris Gutkin, Christopher Lapish, Alexey Kuznetsov. 2016-05-16. Dopamine neurons change the type of excitability in response to stimuli. https://doi.org/10.1101/053637

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