AUTHOR=Wang Yuan , Jin Yi-Kai , Guo Tie-Cheng , Li Zhen-Rong , Feng Bing-Yan , Han Jin-Hong , Vreugdenhil Martin , Lu Cheng-Biao 

TITLE=Activation of Dopamine 4 Receptor Subtype Enhances Gamma Oscillations in Hippocampal Slices of Aged Mice

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.838803

DOI=10.3389/fnagi.2022.838803

ISSN=1663-4365

ABSTRACT=Aim: Neural network oscillation at gamma frequency band (γ oscillation, 30-80Hz) is synchronized synaptic potentials important for higher brain processes and altered in normal ageing. Recent studies indicate that activation of dopamine 4 receptor (DR4) enhanced hippocampal γ oscillation of young mice and fully recovered the impaired hippocampal synaptic plasticity of aged mice, we determined whether this receptor is involved in ageing-related modulation of hippocampal γ oscillation. 
Methods: We recorded γ oscillations in the hippocampal CA3 region from young and aged C57bl6 mice and investigated the effects of dopamine and the selective dopamine receptor (DR) agonists on γ oscillation. 
Results: We first found that γ oscillation power (γ power) was reduced in aged mice compared to young mice, which was restored by exogenous application of dopamine (DA). Second, the selective agonists for different D1- and D2-type dopamine receptors increased γ power in young mice but had little or small effect in aged mice. Third, the D4 receptor (D4R) agonist PD168077 caused a large increase of γ power in aged mice but a small increase in young mice, and its effect is blocked by the highly specific D4R antagonist L-745,870 or largely reduced by a NMDAR antagonist. Fourth, D3R agonist had no effect on γ power of either young or aged mice. 
Conclusion: This study reveals DR subtype-mediated hippocampal γ oscillations is ageing-related and DR4 activation restores the impaired γ oscillations in aged brain, and suggests that D4R is the potential target for the improvement of cognitive deficits related to the ageing and ageing-related diseases.