T-type calcium channels attenuate anxiety in MPTP-treated mice through modulating burst firing of dopaminergic neuron

Abstract

T-type calcium channel(T-VGCC) is a critical voltage-gated channel extensively involved in signal transmission and functional regulation of the nervous system. Recent studies have shown that T-VGCC exhibits low-threshold activation properties and generate high-frequency firing, making it essential in neuronal firing patterns. However, the effects of T-VGCC on dopaminergic (DAergic) neurons in the substantia nigra (SN) remain unclear. In the present study, we constructed Parkinson's disease (PD) model mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and we found that intracerebroventricular injection of T-VGCC blocker (Mibefradil) alleviates the anxiety behavior and the extent of damage to DAergic neurons in MPTP-treated mice. In vivo electrophysiological experiments demonstrated that T-VGCC directly regulates the burst firing of DAergic neurons. Correlation analysis suggested a strong association between DAergic neuron burst firing and anxiety-like behaviors in mice. Notably, calcium imaging experiments revealed that inhibiting T-VGCC significantly decreased calcium signal levels in DAergic neurons of MPTP-treated mice. To sum up, our research results for the first time reveal the crucial role that the burst firing of DAergic neurons in the SN mediated by T-VGCC plays in regulating anxiety behavior in PD. This discovery offers a potential therapeutic target for PD patients with anxiety.