Summary
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.
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.
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More information & hyperlinks
Web resources: | https://cordis.europa.eu/project/id/659927 |
Start date: | 01-05-2015 |
End date: | 30-04-2017 |
Total budget - Public funding: | 160 800,00 Euro - 160 800,00 Euro |
Cordis data
Original description
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.
Status
CLOSEDCall topic
MSCA-IF-2014-EFUpdate Date
28-04-2024
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