Neuregulin and dopamine modulation of hippocampal gamma oscillations is dependent on dopamine D4 receptors. Academic Article uri icon

abstract

  • The neuregulin/ErbB signaling network is genetically associated with schizophrenia and modulates hippocampal oscillations--a type of neuronal network activity important for higher brain processes and altered in psychiatric disorders. Because neuregulin-1 (NRG-1) dramatically increases extracellular dopamine levels in the hippocampus, we investigated the relationship between NRG/ErbB and dopamine signaling in hippocampal oscillations. Using agonists for different D1- and D2-type dopamine receptors, we found that the D4 receptor (D4R) agonist PD168077, but not D1/D5 and D2/D3 agonists, increases oscillation power, and its effect is blocked by the highly specific D4R antagonist L-745,870. Using double in situ hybridization and immunofluorescence histochemistry, we show that hippocampal D4R mRNA and protein are more highly expressed in GAD67-positive GABAergic interneurons, many of which express the NRG-1 receptor ErbB4. Importantly, D4 and ErbB4 receptors are coexpressed in parvalbumin-positive basket cells that are critical for oscillations. Last, we report that D4R activation is essential for the effects of NRG-1 on network activity because L-745,870 and the atypical antipsychotic clozapine dramatically reduce the NRG-1-induced increase in oscillation power. This unique link between D4R and ErbB4 signaling on oscillation power, and their coexpression in parvalbumin-expressing interneurons, suggests a cellular mechanism that may be compromised in different psychiatric disorders affecting cognitive control. These findings are important given the association of a DRD4 polymorphism with alterations in attention, working memory, and oscillations, and suggest potential benefits of D4R modulators for targeting cognitive deficits.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 2

author list (cited authors)

  • Andersson, R. H., Johnston, A., Herman, P. A., Winzer-Serhan, U. H., Karavanova, I., Vullhorst, D., Fisahn, A., & Buonanno, A.

citation count

  • 70

complete list of authors

  • Andersson, Richard H||Johnston, April||Herman, Paul A||Winzer-Serhan, Ursula H||Karavanova, Irina||Vullhorst, Detlef||Fisahn, AndrĂ©||Buonanno, Andres

publication date

  • August 2012