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H2020Individual fellowship2015–2017

SorCSbalance · Role of the sorting receptor SorCS1 in controlling excitation/inhibition balance in neural circuits.

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-05-01 → 2017-04-30
EU contribution
€160,800
Participants
1
Scheme
MSCA-IF

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Results in brief

Role of the sorting receptor SorCS1 in controlling excitation/inhibition balance in neural circuits.

Controlling the precise balance between excitation and inhibition (E/I balance) is critical for information processing in the brain. A perturbed E/I balance has been implicated in the etiology of a wide range of neuropsychiatric disorders. The factors that dictate the balance between excitatory and inhibitory synaptic transmission are still poorly defined, but trans-synaptic interactions between adhesion molecules such as neurexins and neuroligins are thought to be important. We had strong experimental evidence supporting the idea that SorCS1 is a pivotal regulator of synaptic abundance of adhesion molecules, however it was still unclear whether SorCS1 can regulate neuronal function or not. Considering that SorCS1 has also been associated with a variety of neural disorders, including autism, schizophrenia, and Alzheimer’s disease, here I hypothesized that SorCS1 controls E/I balance in the brain by regulating the synaptic abundance of cell surface receptors.

Data: CORDIS, © European Union

Project objective

Controlling the precise balance between excitation and inhibition (E/I balance) is critical for information processing in the brain. A perturbed E/I balance has been implicated in the etiology of a wide range of neuropsychiatric disorders. The factors that dictate the balance between excitatory and inhibitory synaptic transmission are still poorly defined, but trans-synaptic interactions between adhesion molecules such as neurexins and neuroligins are thought to be important. The host laboratory recently identified the sorting receptor SorCS1 as a key regulator of the synaptic abundance of glutamate receptors and adhesion molecules, including neurexins and neuroligins. SorCS1 has been associated with a variety of neural disorders, including autism, schizophrenia, and Alzheimer’s disease. I hypothesize that SorCS1 controls E/I balance in the brain by regulating the synaptic abundance of cell surface receptors. I shall test this hypothesis via the following specific aims:Aim 1: To analyse whether SorCS1 regulates synaptic trafficking of adhesion molecules and neurotransmitter receptors under basal conditions and during synaptic activity.Aim 2: To define how SorCS1 affects excitatory and inhibitory synapse function in vitro and in vivo.Aim 3: To determine whether perturbed SorCS1 levels and disease-associated SorCS1 mutations affect E/I balance in neural circuits.

Original text from CORDIS.

Participants

  • VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium

Links

Data: CORDIS, © European Union