The CNS utilize GABA and glycine as the two main inhibitory neurotransmitters to modulate neuronal excitability and regulate many functions of the human body. Although the location and function of GABA neurons is relatively well studied, the anatomical location of glycinergic neurons remains poorly-defined. In this study, we are interested in the basal ganglia, a brain area that regulate initiation of motor movements and responses that involves cognitive functions such as emotion, vision, some forms of memory and is heavily affected in drug addiction. Among the different structures of the basal ganglia, the GP is enriched in GABAergic nerve terminals that regulate voluntary locomotor activity via the striatopallidal pathway and connections with the thalamus and apparently devoid of glycinergic inputs. In the present study, we use several genetic and biochemical approaches to demonstrate the presence of glycinergic neurons within the basal ganglia. Our data provide evidence of a novel inhibitory glycinergic circuit, where the cell bodies are localized to the substantia nigra pars compacta (SNc) and projections moving along the medial forebrain bundle to finally innervate GP. These glycinergic neurons showed immune-reactivity for GAD67 and NeuN, suggesting a dual GABA/Glycine phenotype. Western blot analysis, immunohistochemistry and electrophysiology analysis demonstrate the presence of the glycine receptor in the GP and confirm the inhibitory nature on these synapses. This application will reveal the role of these nigropallidal glycinergic fibers in the control of specific basal-ganglia regulated behaviors.

Public Health Relevance

Glycinergic neurotransmission is a critical component in the modulation of a variety of sensory and motor information such as pain transmission and voluntary movement. This research seeks to provide fundamental knowledge about the location and connections of glycinergic neurons in the CNS and increase our understanding of motor dysfunctions in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Enhancement Award (SC1)
Project #
1SC1NS119056-01
Application #
9855940
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Chen, Daofen
Project Start
2020-05-15
Project End
2024-04-30
Budget Start
2020-05-15
Budget End
2021-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Texas El Paso
Department
Type
DUNS #
132051285
City
El Paso
State
TX
Country
United States
Zip Code
79968