Dopamine neuron dependent behaviours mediated by glutamate cotransmission

Susana Mingote, Nao Chuhma, Abigail Kalmbach, Gretchen M. Thomsen, Yvonne Wang, Andra Mihali, Caroline Sferrazza, Ilana Zucker-Scharff, Anna Claire Siena, Martha G. Welch, José Lizardi-Ortiz, David Sulzer, Holly Moore, Inna Gaisler-Salomon, Stephen Rayport

Research output: Contribution to journalArticlepeer-review

Abstract

Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter. To elucidate the behavioral role of the cotransmission, we targeted the glutamate-recycling enzyme glutaminase (gene Gls1). In mice with a dopamine transporter (Slc6a3)-driven conditional heterozygous (cHET) reduction of Gls1 in their dopamine neurons, dopamine neuron survival and transmission were unaffected, while glutamate cotransmission at phasic firing frequencies was reduced, enabling a selective focus on the cotransmission. The mice showed normal emotional and motor behaviors, and an unaffected response to acute amphetamine. Strikingly, amphetamine sensitization was reduced and latent inhibition potentiated. These behavioral effects, also seen in global GLS1 HETs with a schizophrenia resilience phenotype, were not seen in mice with an Emx1- driven forebrain reduction affecting most brain glutamatergic neurons. Thus, a reduction in dopamine neuron glutamate cotransmission appears to mediate significant components of the GLS1 HET schizophrenia resilience phenotype, and glutamate cotransmission appears to be important in attribution of motivational salience.

Original languageEnglish
Article numbere27566
JournaleLife
Volume6
DOIs
StatePublished - 13 Jul 2017

Bibliographical note

Publisher Copyright:
© Mingote et al.

Keywords

  • Amphetamine sensitization
  • Glutaminase
  • Latent inhibition
  • Motivational salience
  • Mouse
  • Resilience model
  • Schizophrenia

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Neuroscience

Fingerprint

Dive into the research topics of 'Dopamine neuron dependent behaviours mediated by glutamate cotransmission'. Together they form a unique fingerprint.

Cite this