Glutamatergic neurotransmission: A potential pharmacotherapeutic target for the treatment of cognitive disorders

In the mammalian brain, glutamate is regarded to be the primary excitatory neurotransmitter due to its wide-spread distribution and wide range of metabolic functions. Glutamate plays key roles in regulating neurogenesis, synaptogenesis, neurite outgrowth, and neuron survival in the brain. Ionotropic and metabotropic glutamate receptors, neurotransmitters, neurotensin, neurosteroids, and others co-ordinately formulate a complex gluta-matergic network in the brain that maintains optimal excitatory neurotransmission. Cognitive activities are potentially synchronized by the glutamatergic activities in the brain via restoring synaptic plasticity. Dysfunc-tional glutamate receptors and other glutamatergic components are responsible for the aberrant glutamatergic activity in the brain that cause cognitive impairments, loss of synaptic plasticity, and neuronal damage. Thus, controlling the brain's glutamatergic transmission and modifying glutamate receptor function could be a po-tential therapeutic strategy for cognitive disorders. Certain drugs that regulate glutamate receptor activities have shown therapeutic promise in improving cognitive functions in preclinical and clinical studies. However, several issues regarding precise functional information of glutamatergic activity are yet to be comprehensively