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Dopamine release dynamics in the tuberoinfundibular dopamine system

Stagkourakis, Stefanos and Dunevall, Johan and Taleat, Zahra and Ewing, Andrew G. and Broberger, Christian (2019) Dopamine release dynamics in the tuberoinfundibular dopamine system. Journal of Neuroscience, 39 (21). pp. 4009-4022. ISSN 0270-6474. PMCID PMC6529860. doi:10.1523/jneurosci.2339-18.2019.

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The relationship between neuronal impulse activity and neurotransmitter release remains elusive. This issue is especially poorly understood in the neuroendocrine system, with its particular demands on periodically voluminous release of neurohormones at the interface of axon terminals and vasculature. A shortage of techniques with sufficient temporal resolution has hindered real-time monitoring of the secretion of the peptides that dominate among the neurohormones. The lactotropic axis provides an important exception in neurochemical identity, however, as pituitary prolactin secretion is primarily under monoaminergic control, via tuberoinfundibular dopamine (TIDA) neurons projecting to the median eminence (ME). Here, we combined electrical or optogenetic stimulation and fast-scan cyclic voltammetry to address dopamine release dynamics in the male mouse TIDA system. Imposing different discharge frequencies during brief (3 s) stimulation of TIDA terminals in the ME revealed that dopamine output is maximal at 10 Hz, which was found to parallel the TIDA neuron action potential frequency distribution during phasic discharge. Over more sustained stimulation periods (150 s), maximal output occurred at 5 Hz, similar to the average action potential firing frequency of tonically active TIDA neurons. Application of the dopamine transporter blocker, methylphenidate, significantly increased dopamine levels in the ME, supporting a functional role of the transporter at the neurons' terminals. Lastly, TIDA neuron stimulation at the cell body yielded perisomatic release of dopamine, which may contribute to an ultrafast negative feedback mechanism to constrain TIDA electrical activity. Together, these data shed light on how spiking patterns in the neuroendocrine system translate to vesicular release toward the pituitary and identify how dopamine dynamics are controlled in the TIDA system at different cellular compartments.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Stagkourakis, Stefanos0000-0003-1218-791X
Dunevall, Johan0000-0001-9188-9893
Taleat, Zahra0000-0003-4399-1644
Broberger, Christian0000-0002-7050-8809
Additional Information:© 2019 the authors. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received Sept. 11, 2018; revised Jan. 6, 2019; accepted Jan. 9, 2019. This work was supported by European Research Council Starting Grant ENDOSWITCH 261286, Swedish Research Council 2014–3906, Strategic Research Program in Diabetes at Karolinska Institutet, Hjärnfonden (Swedish Brain Foundation), Novo Nordisk Fonden, Karolinska Institutet internal funds to C.B., European Research Council Advanced Grant, and the Swedish Research Council and the Knut and Alice Wallenberg Foundation to A.G.E. We thank Paul Williams for providing insightful suggestions on the manuscript; Elin Dahlberg and Sandra Azami for expert technical support; and Dr. Nils-Göran Larsson for generously sharing DAT-Cre mice. The authors declare no competing financial interests.
Funding AgencyGrant Number
European Research Council (ERC)261286
Swedish Research Council2014-3906
Swedish Brain FoundationUNSPECIFIED
Novo Nordisk FondenUNSPECIFIED
Karolinska InstitutetUNSPECIFIED
Knut and Alice Wallenberg FoundationUNSPECIFIED
Subject Keywords:arcuate nucleus; dopamine release; frequency coding; FSCV; hypothalamus; tuberoinfundibular
Issue or Number:21
PubMed Central ID:PMC6529860
Record Number:CaltechAUTHORS:20190522-154638287
Persistent URL:
Official Citation:Dopamine Release Dynamics in the Tuberoinfundibular Dopamine System Stefanos Stagkourakis, Johan Dunevall, Zahra Taleat, Andrew G. Ewing, Christian Broberger Journal of Neuroscience 22 May 2019, 39 (21) 4009-4022; DOI: 10.1523/JNEUROSCI.2339-18.2019
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95716
Deposited By: George Porter
Deposited On:22 May 2019 23:15
Last Modified:16 Nov 2021 17:14

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