Up next in the neurotransmitter series….glutamate: the primary excitatory neurotransmitter in the central nervous system(CNS).
- Glutamate is found in approximately 70% of CNS synapses.
- Glutamate has the ability to drive synaptic transmission in many many synapses because it can bind to multiple receptors, which will modulate whether the neuronal response will be fast or slow.
- For example, Glutamate receptors can be either ionotropic or or ligand-gated (which basically means that they are transmembrane ion channels that open and close in response to a chemical) or metabotropic, G-protein coupled receptors, which are transmembrane receptors that activate signal transduction pathways once they sense a chemical messenger (i.e. neurotransmitter). Ionotropic receptor action tends to be faster than metabotropic receptor action because metabotropic receptors often require second messenger pathways.
- Ionotropic glutamate receptors include: NMDA receptors, AMPA receptors, and Kainate receptors.
- Glutamate plays an important role in neuronal differentiation, migration, and survival in the developing brain by facilitating Ca+2 entry into the cell.
- Additionally, glutamate neurotransmission plays crucial roles in synapse formation and elimination.
- Neurodegeneration in late onset disorders, such as Huntington’s, Parkinson’s and Alzheimer’s disease, is thought to be partially dependent on endogenous glutamatergic neurotransmission. (Some glutamate receptors may have excitotoxic effects-enhanced AMPA activation). In short, although glutamate is essential for neuronal function, it can also be toxic.
- Deficits/dysregulation in glutamate neurotransmission and glutamate receptor action are also implicated in Fragile X syndrome (a mental retardation subtype)
- Glutamate, along with acetylcholine and GABA, are considered small neurotransmitter molecules and are contained in small clear core vesicles. As such, they are synthesized directly in the axon terminal, near their release sites.
- Glutamate is synthesized from a glucose precursor-glutamine. Glutaminase is the enzyme that turns glutamine into glutamate.
- Glutamate degradation occurs by reuptake in the post-synaptic cell. Once in the post-synaptic cell, a glutamate synthase can make glutamine (the precursor for glutamate) that can be transported back to the pre-synaptic cell in order to be made into glutamate again by glutaminase.
Sources:
Danbolt, NC. Glutamate as a Neurotransmitter: Overview
Meldrum, BS. 2000. Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology. Journal of Nutrition.
Rice, Margaret. Neurotransmitter Definition and Criteria. Lecture given as part of Cellular Neuroscience course, Fall 2010.
Ziff, Ed. Synapse Function and Formation in CNS. Lecture given as part of Developmental Neuroscience course, Spring 2010.
