After acquiring a diploma as biological pharmacist from the Belgrade University in Serbia, Senka Hadzibegovic obtained an Erasmus Mundus fellowship to join the neuroscience community in Bordeaux,France to pursuit her Ph.D. During her doctoral studies, under the supervision of Bruno Bontempi from the Institute of Neurodegenerative Diseases (IMN) in Bordeaux, she used different approaches, ranging from behavioral to molecular analysis in a mouse model of Alzheimer’s disease (AD) to identify new markers of AD. Her work pointed to a crucial involvement of hippocampal oscillations called sharp-wave ripples in spatial memory formation and identified amyloid-β induced impairment in dynamics of these ripples as a mechanism responsible for the spatial memory deficits associated with AD. At the molecular level she was successful in establishing that amyloid-β destabilizes synaptic organization and increases an extrasynaptic pool of GluN2B-containing NMDA receptors, a reorganization that translates into impaired memory formation. She presented her work at international conferences obtaining awards for best poster and presentation. As a postdoctoral researcher in the Frick Lab in Bordeaux, she has been studying the neuronal allocation mechanisms of remote memories in under physiological conditions and in two mouse models of AD. Thus, an important driving force of her research is to understand the molecular and cellular processes underlying memory formation and to identify changes that can explain memory deficits associated with AD.

Principal Investigator: Andreas Frick

Fellow: Elina Coudroy

Undergraduate Fellow Project: Changes in intrinsic excitability of prefrontal cortex underlie early cognitive impairment in Alzheimer’s disease

Rapid forgetting is an early symptom of Alzheimer’s disease (AD) that correlates with amyloid-ß accumulation in the prefrontal cortex (PFC). Data from our group show that associative learning tasks recruit specific PFC neuron populations and trigger plasticity in the intrinsic excitability/ion channels of these neurons as crucial cellular mechanism of long-term memory storage. We also found that amyloid-ß alters the function of these ion channels in PFC neurons. We hypothesize that abnormal excitability causes dysfunction of PFC network activity and crucial cellular memory mechanisms, resulting in a disruption of long-term memory storage and thus faster forgetting. The overall goal of our proposal is to characterize the impact of amyloid-ß on the activity of PFC neuronal ensembles at cellular resolution during different phases of memory formation. Further, we want to probe the consequences of modulating the excitability of PFC engram neurons for correcting deficits in memory performance, as well as network activity. These neuronal activity measures will enable us to evaluate therapeutic strategies targeting ion channels as promising therapeutic targets in early-phase AD. We will use a highly innovative approach combining associative memory tasks with novel viral tool-based approaches, transgenic mice, electrophysiology, and qPCR approaches.