Glutamatergic transmission

Glutamatergic transmission is the primary excitatory signaling mechanism in the mammalian central nervous system, utilizing the amino acid L-glutamate as its neurotransmitter (Purves et al., Neuroscience, 2018). It encompasses a diverse array of molecular targets, including ionotropic glutamate receptors (NMDA, AMPA, and kainate receptors) which mediate rapid ion flux, and metabotropic G protein-coupled receptors (mGluRs) that regulate slower neuromodulatory effects (Traynelis et al., Pharmacol Rev, 2010). This system is essential for neuroplasticity, memory formation, and overall brain connectivity. Dysregulation of glutamatergic signaling is a hallmark of various pathologies; for instance, glutamate excitotoxicity contributes to neuronal death in stroke and Amyotrophic Lateral Sclerosis (ALS), while NMDA receptor hypofunction is a leading hypothesis in the pathophysiology of schizophrenia (Marsman et al., Schizophr Bull, 2013). Pharmacological agents like memantine and ketamine target these receptors to treat Alzheimer's disease and treatment-resistant depression, respectively. However, the ubiquitous nature of glutamate in the brain presents significant therapeutic challenges, as broad modulation can lead to severe side effects such as dissociation, hallucinations, or neurotoxicity.

Other names

Glutamate signalingExcitatory neurotransmissionGlutamatergic systemGlutamate-mediated synaptic transmission

Modulation of ionotropic (NMDA, AMPA, Kainate) and metabotropic (mGluR) receptors, inhibition of presynaptic glutamate release, or enhancement of glial glutamate uptake via excitatory amino acid transporters (EAATs).