Descripción del proyecto
Nueva visión sobre las transmisiones sinápticas en el encéfalo
Las neuronas del encéfalo se comunican a través de sinapsis, donde la señal eléctrica pasa de una célula a la siguiente mediante la unión de neurotransmisores a los receptores de la membrana. El receptor ácido N-metil-D-aspártico (NMDA, por sus siglas en inglés) es un canal iónico cerrado por el glutamato que se ha asociado a la plasticidad neuronal. Tradicionalmente, se sabe que el mecanismo implica la unión del glutamato al receptor, que desencadena un flujo de calcio. Los científicos del proyecto NovelNMDA, financiado con fondos europeos, han descubierto que el NMDA puede funcionar a través de un mecanismo de señalización no iónico. Se espera que una investigación más profunda del proceso mejore nuestra comprensión de la señalización sináptica.
Objetivo
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.
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Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
37075 Goettingen
Alemania