Department of Neurosciences, Laboratory of Neuro- and Psychophysiology, KU Leuven Medical School, Leuven 3000, Belgium.
Leuven Brain Institute, KU Leuven, Leuven 3000, Belgium.
Cereb Cortex. 2020 Jun 30;30(8):4281-4296. doi: 10.1093/cercor/bhaa007.
The ventral tegmental area (VTA) is a midbrain structure at the heart of the dopaminergic system underlying adaptive behavior. Endogenous firing rates of dopamine cells in the VTA vary from fast phasic bursts to slow tonic activity. Artificial perturbations of the VTA, through electrical or optogenetic stimulation methods, generate different and sometimes even contrasting behavioral outcomes depending on stimulation parameters such as frequency, amplitude, and pulse width. Here, we investigate the global functional effects of electrical stimulation frequency (10, 20, 50, and 100 Hz) of the VTA in rhesus monkeys. We stimulated 2 animals with chronic electrodes, either awake or anesthetized, while concurrently acquiring whole-brain functional magnetic resonance imaging (fMRI) signals. In the awake state, activity as a function of stimulation frequency followed an inverted U-shape in many cortical and subcortical structures, with highest activity observed at 20 and 50 Hz and lower activity at 10 and 100 Hz. Under anesthesia, the hemodynamic responses in connected brain areas were slightly positive at 10 Hz stimulation, but decreased linearly as a function of higher stimulation frequencies. A speculative explanation for the remarkable frequency dependence of stimulation-induced fMRI activity is that the VTA makes use of different frequency channels to communicate with different postsynaptic sites.
腹侧被盖区(VTA)是中脑结构,位于适应行为的多巴胺能系统的核心。VTA 中的多巴胺细胞的内源性放电率从快速相位爆发到缓慢的紧张活动不等。通过电或光遗传学刺激方法对 VTA 的人工干扰会根据刺激参数(如频率、幅度和脉冲宽度)产生不同的、有时甚至是相反的行为结果。在这里,我们研究了恒河猴 VTA 电刺激频率(10、20、50 和 100 Hz)的全局功能影响。我们使用慢性电极对 2 只动物进行刺激,无论是在清醒状态还是麻醉状态下,同时获取全脑功能磁共振成像(fMRI)信号。在清醒状态下,许多皮质和皮质下结构的活动随刺激频率呈倒 U 形变化,在 20 和 50 Hz 时观察到最高活动,而在 10 和 100 Hz 时活动较低。在麻醉状态下,10 Hz 刺激时连接脑区的血液动力学反应略有正性,但随着更高刺激频率的增加呈线性下降。对刺激诱导 fMRI 活动的显著频率依赖性的一种推测性解释是,VTA 利用不同的频率通道与不同的突触后位点进行通信。