Projektbeschreibung
Neue Perspektive auf die synaptische Übertragung im Gehirn
Die Neuronen im Gehirn kommunizieren über Synapsen, an denen elektrische Signale von einer Zelle auf die nächste übergehen, indem Neurotransmitter an Membranrezeptoren gebunden werden. Der NMDA-Rezeptor ist ein glutamatgesteuerter Ionenkanal, der mit neuronaler Plastizität in Zusammenhang steht. Dieser Mechanismus umfasst die Bindung von Glutamat an den Rezeptor, was einen Kalziumfluss auslöst. Das Team des EU-finanzierten Projekts NovelNMDA hat herausgefunden, das NMDA über einen nicht-ionischen Signalmechanismus ablaufen könnte. Eine weitere Analyse des Prozesses könnte unser Verständnis der synaptischen Signalgebung erweitern.
Ziel
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.
Wissenschaftliches Gebiet
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Finanzierungsplan
ERC-STG - Starting GrantGastgebende Einrichtung
37075 Goettingen
Deutschland