Glutamate Signaling and Homeostasis in the Central Nervous System

Glutamate is the main excitatory neurotransmitter in the vertebrate central nervous system. In order to ensure faithful synaptic transmission and to prevent excitotoxicity (death of neurons due to excessive stimulation by neurotransmission), the synaptic concentration of glutamate needs to be tightly regulated. This is achieved by a group of glutamate transporters (excitatory amino acid transporter, EAAT) that are expressed both on glia cells and neurons.

These transporters can also influence the membrane potential of the cell by inducing an anion conductance (chloride) that can hyperpolarize the cell. In the retina these transporters have multiples roles in stabilizing the membrane potential of presynaptic neurons, synaptic clearance, and direct synaptic transmission. The last aspect is unusual since glutamate effectively functions as an inhibitory neurotransmitter in such a context. Such inhibitory neural transmission can also be mediated by metabotropic glutamate receptors (mGluR). We found evidence that such inhibitory action may not be confined to the retina.

An imbalance of excitatory and inhibitory synaptic transmission can lead to overactivation of the brain, resulting in epileptic seizures. We found that defects of glutamate homeostasis can lead to generalized seizures. We are currently investigating the role of glial and neuronal cells in the initiation and spreading of such epileptic events.

People involved:

Dr. Marion Haug

Adriana Hotz, MSc

Selected publications:

Niklaus S, Cadetti L, Vom Berg-Maurer CM, Lehnherr A, Hotz AL, Forster IC, Gesemann M, Neuhauss SCF (2017). Shaping of Signal Transmission at the Photoreceptor Synapse by EAAT2 Glutamate Transporters. eNeuro 4(3). doi: 10.1523

Glasauer SMK, Wäger R, Gesemann M, Neuhauss SCF* (2016). mglur6b:EGFP transgenic zebrafish suggest novel functions of metabotropic glutamate signaling in retina and other brain regions. Journal of Comparative Neurology, 524(12):2363-78