LSA Fellows 10 

Project titel: Role of Bassoon in interneuron (dys-)function related to neuropsychiatric disorders Projectleader: Dr. Anil Annamneedi

Proper functioning of the brain depends upon tight connections between neurons called synapses, which transfer information via neurotransmitters. The neurotransmitter release side of the synapse is the presynapse and information receiving side is the postsynapse. Both the synaptic sides are composed of complex machinery of proteins, which are important for the normal cognitive performance of the brain. Under many diseased conditions synaptic proteins are dysregulated leading to impairment of brain function.

To date, the consequences of presynaptic proteins’ dysfunction for disease progression is poorly understood. So the important rationale of this project is to identify the contributions of the presynaptic scaffolding protein Bassoon during the development of the cognitive dysfunctions in neuropsychiatric conditions including schizophrenia. The brain is composed of excitatory, inhibitory and modulatory neuronal systems. Dysregulation of the inhibitory GABAergic interneuron system has been disclosed as an important mechanism in schizophrenia. The GABAergic system is composed of many subtypes and parvalbumin expressing (PV+) interneurons are the large and important population. PV+ interneurons mediate complex cognitive functions and are frequently prone to pathological modifications under neuropsychiatric conditions. Making use of conditional knockout mouse technology, I would like to study the role of Bassoon protein in PV+ interneuron-mediated cognitive functions and their presynaptic changes under neuropsychiatric cognitive dysfunction.

Besides understanding the presynaptic mechanisms of PV+ interneuron-mediated dysfunction, this study will also allow to develop therapeutic strategies in the future, based on pharmacological interventions in animal models.