Characterization of a novel phenotypic neurotransmitter plasticity in the central nervous system
Open Access
- Author:
- Tuncdemir, Sebnem Nur
- Graduate Program:
- Biology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- July 16, 2008
- Committee Members:
- Gong Chen, Thesis Advisor/Co-Advisor
- Keywords:
- glycine
GABA
Inducible plasticity
co-transmission - Abstract:
- Neurotransmitter phenotype for a given neuron is determined not only by intrinsic but also extrinsic factors during development. While intrinsic factors might be responsible for the majority of neurotransmitter phenotype, the role of extrinsic factors has been explored but the underlying molecular mechanism remains largely unknown. Here, we report an inducible plasticity of inhibitory neurotransmitter phenotype after alteration of postsynaptic receptors together with cell adhesion molecules. In embryonic hypothalamic cultures, inhibitory neurotransmission is mediated by GABAergic neurons only. Although no glycinergic currents can be detected in pure neuronal cultures, functional glycinergic synapses are inducible in cocultured HEK 293T cells expressing glycine receptors (GlyRs) and a cell adhesion molecule neuroligin-2 (NL-2). In fact, mixed GABAergic and glycinergic synapses are formed on HEK 293T cells that co-express NL-2, GlyRs and GABAA-Rs. Importantly, hypothalamic neurons do express high level of GlyRs in addition to GABAA-Rs. Ectopic expression of NL-2 or GlyRs alone in hypothalamic neurons cannot change the GABAergic transmitter phenotype. However, coexpression of NL-2 and GlyRs in hypothalamic neurons induces robust functional glycinergic synapses in hypothalamic cultures. Moreover, both homomeric and heteromeric GlyRs can be clustered at the postsynaptic sites of induced synapses. Our data reveal that molecular manipulation of postsynaptic receptor organization, not receptor expression, is critical in altering the neurotransmission phenotype. Such inducible plasticity in central neurons also suggests that brain function is much flexible in adapting to extrinsic signals.