Date of Award

2016-01-01

Degree Name

Master of Science

Department

Biological Sciences

Advisor(s)

Manuel Miranda-Arango

Abstract

Glycinergic neurotransmission is essential for the function of sensory and motor systems associated with pain transmission and rhythmic motor patterns. Yet, the way glycinergic circuits modulates motor systems via the globus pallidus external (GPe) is not clear. The cyto-architecture of glycinergic circuitry is poorly understood and most work has focused in brainstem areas. It is believed that glycinergic neurons are mainly interneurons regulating local circuits. However, it is now becoming clear that they are also projection neurons, constituting true neuronal circuits. At the glycinergic synapse, termination of neurotransmission and recycling of glycine is regulated by two transporters, glycine transporter 1 (GlyT1) and glycine transporter 2 (GlyT2). GlyT1 and GlyT2 are both expressed in the cerebellum, brainstem and throughout the spinal cord. In addition to those areas, GlyT1 is expressed in subcortical forebrain regions and the midbrain. GlyTs are essential for survival and knockout of either gene leads to animal death shortly after birth, due to impaired breathing and muscular spasm. Based on our preliminary results, glycinergic neurons expressing GlyT1 are found within structures of the basal ganglia, a brain area involved in somatosensory integration, voluntary motor movement and an array of diverse cognitive functions. Preliminary results also demonstrate that GlyT1 immunoreactivity co-localize with GAD67, suggesting a dual phenotype, GABAergic and glycinergic. Interestingly, the physiological role of these neurons containing and releasing both inhibitory neurotransmitters remains unknown and deserves further investigation. Thus, the overarching hypoThesis is that these putative glycinergic neurons help modulate critical basal ganglia function via regulation of a novel nigropallidal pathway. To test this hypoThesis, we used fluorescent dyes and viral tracing techniques to outline glycinergic neuronal projections to the GPe. Given the role of the GPe in voluntary motor movement, the results from this project have significant potential to inform the development of new therapeutic approaches for basal ganglia-related disorders such as Parkinsonâ??s disease (PD) and Huntingtonâ??s chorea.

Language

en

Provenance

Received from ProQuest

File Size

41 pages

File Format

application/pdf

Rights Holder

Rosalia Ortega

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