1. Academic Validation
  2. MPTP-Induced Dopamine Depletion in Basolateral Amygdala via Decrease of D2R Activation Suppresses GABAA Receptors Expression and LTD Induction Leading to Anxiety-Like Behaviors

MPTP-Induced Dopamine Depletion in Basolateral Amygdala via Decrease of D2R Activation Suppresses GABAA Receptors Expression and LTD Induction Leading to Anxiety-Like Behaviors

  • Front Mol Neurosci. 2017 Aug 7;10:247. doi: 10.3389/fnmol.2017.00247.
Tingting Zhang 1 2 Tingting Chen 1 2 Peipei Chen 2 Baofeng Zhang 2 Juan Hong 1 2 Ling Chen 1 2
Affiliations

Affiliations

  • 1 State Key Lab of Reproductive Medicine, Nanjing Medical UniversityNanjing, China.
  • 2 Department of Physiology, Nanjing Medical UniversityNanjing, China.
Abstract

Anxiety disorders commonly occur in Parkinson's disease. Using field potential recording and patch-clamp recording, we evaluated influence of MPTP-reduced dopaminergic afferent in basolateral amygdala (BLA), a main region for affective regulation, on excitatory-inhibitory circuits and synaptic plasticity. Field excitatory post-synaptic potential (fEPSP) slopes at external capsule-BLA synapses were increased in MPTP-mice with decreases in paired-pulse facilitation and long-term potentiation amplitude, which were corrected by bath-application of D2R agonist quinpirole or cannabinoid type 1 receptors agonist WIN55,212-2, but not D1R agonist SKF38393. Compared to single waveform fEPSP in control mice, a multi-spike waveform fEPSP was observed in MPTP-mice with prolongation of duration and an increase in paired-pulse inhibition, which were recovered by BLA-injection of quinpirole for 2 days rather than bath-application. Density of GABA-evoked current (IGABA) in BLA principal neurons and GABAAR-α2 subunit expression were reduced in MPTP-mice, which were recovered by administration of quinpirole. Decline of PKC phosphorylation in BLA of MPTP-mice was corrected by bath-application of quinpirole, but not SKF38393. In MPTP-mice, BLA-injection of quinpirole or PKC Activator PMA could recover GABAAR expression, which was sensitive to PKC Inhibitor GF109203X. The impairment of long-term depression (LTD) in MPTP-mice was rescued by bath-application of GABAAR agonist muscimol or BLA-injection of quinpirole and PMA. Finally, BLA-injection of muscimol, quinpirole or PMA relieved anxiety-like behaviors in MPTP-mice. The results indicate that the MPTP-induced dopamine depletion in BLA principal neurons through reducing D2R-mediated PKC phosphorylation suppresses GABAAR expression and activity, which impairs GABAAR-mediated inhibition and LTD induction leading to anxiety-like behaviors.

Keywords

GABAA receptor (GABAAR); anxiety-like behaviors; basolateral amygdala (BLA); dopaminergic receptor (DR); synaptic plasticity.

Figures
Products