Abstract
The human substantia nigra (SN) is thought to consist of two functionally distinct neuronal populations—dopaminergic (DA) neurons in the pars compacta subregion and GABA-ergic neurons in the pars reticulata subregion. However, a functional dissociation between these neuronal populations has not previously been demonstrated in the awake human. Here we obtained microelectrode recordings from the SN of patients undergoing deep brain stimulation (DBS) surgery for Parkinson's disease as they performed a two-alternative reinforcement learning task. Following positive feedback presentation, we found that putative DA and GABA neurons demonstrated distinct temporal dynamics. DA neurons demonstrated phasic increases in activity (250–500 ms post-feedback) whereas putative GABA neurons demonstrated more delayed and sustained increases in activity (500–1000 ms post-feedback). These results provide the first electrophysiological evidence for a functional dissociation between DA and GABA neurons in the human SN. We discuss possible functions for these neuronal responses based on previous findings in human and animal studies.
Highlights
Animal studies have shown that the substantia nigra (SN) consists of two functionally distinct neuronal populations— dopaminergic (DA) neurons in the pars compacta subregion and GABA-ergic neurons in the pars reticulata subregion
DA neurons demonstrated phasic increases in activity (250–500 ms post-feedback) whereas putative GABA neurons demonstrated more delayed and sustained increases in activity (500–1000 ms post-feedback). These results provide the first electrophysiological evidence for a functional dissociation between DA and GABA neurons in the human SN
We identified putative DA and GABA neurons based on the physiological properties of their extracellular waveforms, and compared the functional properties of the two populations during the task
Summary
Animal studies have shown that the substantia nigra (SN) consists of two functionally distinct neuronal populations— dopaminergic (DA) neurons in the pars compacta subregion and GABA-ergic neurons in the pars reticulata subregion. DA neurons have been shown to encode reward prediction errors with phasic bursts of firing, that occur when there is a mismatch between obtained and expected outcomes (Schultz et al, 1997; Bayer and Glimcher, 2005) These DA bursts are thought to guide reinforcement learning by adjusting synaptic strength in downstream regions following unexpected outcomes (Reynolds et al, 2001; Tsai et al, 2009). GABA neurons are involved in inhibitory regulation of various brain structures including frontal cortical regions (via the thalamus), premotor brainstem nuclei and midbrain DA neurons (Carpenter et al, 1976; Hikosaka and Wurtz, 1983; Tepper et al, 1995; Henny et al, 2012) Despite these advances in the animal, the functional role of human SN neurons has not been elucidated. Histochemical studies have shown that DA and GABA neurons co-exist in the human SN (Damier et al, 1999a), a functional dissociation between these SN neural populations has not previously been demonstrated
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