Glutamate and potassium (K) are released during neuronal firing and need to be tightly regulated to ensure accurate synaptic transmission. We recently described that they interact, demonstrating K-dependent glutamate transporter inhibition. Analogous to the pharmacological inhibition of the glutamate transporter, which decreases neuronal transmission via extrasynaptic glutamate spillover and subsequent activation of metabotropic glutamate receptors (mGluRs), we found that increasing the levels of extracellular K also causes decreased neuronal synaptic vesicle release that is prevented by group II mGluR inhibition. We are now studying this novel, previously unreported physiological activity-dependent modulation of synaptic activity in spontaneous and evoked oscillations of the neuronal network. For this, we are developing novel tools such as fluorescent nanosensors and astrocyte-specific viral brain gene delivery.
RESEARCH & TECHNOLOGY
- Potassium and glutamate interplay for neuronal network activity: an extracellular point of view.
- Regulation of neuronal activity by lactate receptor activation: basic and translational studies in mouse and human brain tissue
Potassium and glutamate interplay for neuronal network activity: an extracellular point of view.
Regulation of neuronal activity by lactate receptor activation: basic and translational studies in mouse and human brain tissue
Lactate is increasingly recognized as an energy substrate for neurons. Besides this still debated metabolic role, lactate, while in the extracellular space, may exert other actions on brain cells. Recent studies have documented that lactate also influences neuronal activity by a receptor-mediated non-metabolic mechanism. This confers additional roles for lactate as a signaling molecule for neurons. We provided the first evidence for a functional implication of the lactate receptor in cultured cortical neurons. We are now characterizing these signaling pathways in mouse neurons in primary cultures and acute brain slices using both calcium imaging and patch-clamp. We are also investigating the potential importance of the receptor and selected agonists in fresh human brain tissue with an emphasis on epilepsy.
Human neuronal activity measured using calcium imaging (Fluo-8)