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Cell Rep. 2016 Apr 26;15(4):735-747. doi: 10.1016/j.celrep.2016.03.062. Epub 2016 Apr 14.

Dopamine Autoreceptor Regulation of a Hypothalamic Dopaminergic Network.

Cell reports

Stefanos Stagkourakis, Hoseok Kim, David J Lyons, Christian Broberger

Affiliations

  1. Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address: [email protected].
  2. Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
  3. Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address: [email protected].

PMID: 27149844 PMCID: PMC4850423 DOI: 10.1016/j.celrep.2016.03.062

Abstract

How autoreceptors contribute to maintaining a stable output of rhythmically active neuronal circuits is poorly understood. Here, we examine this issue in a dopamine population, spontaneously oscillating hypothalamic rat (TIDA) neurons, that underlie neuroendocrine control of reproduction and neuroleptic side effects. Activation of dopamine receptors of the type 2 family (D2Rs) at the cell-body level slowed TIDA oscillations through two mechanisms. First, they prolonged the depolarizing phase through a combination of presynaptic increases in inhibition and postsynaptic hyperpolarization. Second, they extended the discharge phase through presynaptic attenuation of calcium currents and decreased synaptic inhibition. Dopamine reuptake blockade similarly reconfigured the oscillation, indicating that ambient somatodendritic transmitter concentration determines electrical behavior. In the absence of D2R feedback, however, discharge was abolished by depolarization block. These results indicate the existence of an ultra-short feedback loop whereby neuroendocrine dopamine neurons tune network behavior to echoes of their own activity, reflected in ambient somatodendritic dopamine, and also suggest a mechanism for antipsychotic side effects.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: D2 receptor; arcuate nucleus; auto-inhibition; calcium currents; network oscillation; prolactin; tuberoinfundibular

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