Project description
Novel view on synaptic transmission in the brain
Neurons in the brain communicate through synapses where the electrical signal passes from one cell to the next through the binding of neurotransmitters to membrane receptors. The NMDA receptor is a glutamate-gated ion channel that has been associated with neuronal plasticity. The mechanism is traditionally known to involve the binding of glutamate to the receptor, which triggers a flux of calcium. Scientists of the EU-funded NovelNMDA project have discovered that NMDA may function through a non-ionic signalling mechanism. Further investigation into the process is expected to improve our understanding of synaptic signalling.
Objective
Long-term synaptic plasticity is an experience dependent increase or decrease in synaptic signaling between nerve cells that can last from hours to days or even longer. It is thought to represent the cellular substrate of learning and memory by providing an information storage mechanism in the brain. At many excitatory synapses, plasticity-induction processes involve NMDA receptors, glutamate-gated ion channels. I recently discovered a new form of NMDA receptor signaling during spike-timing dependent long-term depression at layer-4-to-layer-2/3 synapses in rodent somatosensory cortex, which requires glutamate binding to the NMDA receptor but not ion flux through its channel. This non-ionic signaling mechanism via the NMDA receptor represents a strikingly overlooked signaling pathway at glutamatergic synapses, and its discovery may overturn much of the long-term depression field, which has focused on calcium influx through the NMDA receptors as the relevant signal in plasticity. Indeed, the discovery of non-ionic NMDA receptor signaling in the postsynaptic membrane even calls into question our current understanding of the basic properties of synaptic signaling.
By combining electrophysiology and two-photon imaging and uncaging, we will address the fundamental properties of non-ionic NMDAR dependent plasticity at cortical layer-4-to-layer-2/3 synapses, determine in which synaptic subcompartment plasticity occurs, assess whether signaling depends on a particular NMDA receptor subtype, and examine whether non-ionic NMDA receptor signaling represents a general mechanism at other glutamatergic synapses. This work will lead to a detailed functional understanding of the novel non-ionic NMDA receptor signaling process and its role in synapse function and plasticity.
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
37075 Goettingen
Germany