Giusy Pizzirusso

Medical Doctor and Ph.D. student
I am a medical doctor and Ph.D. student. My Ph.D. project is part of the
KI-NIH Doctoral Partnership Programme in Neuroscience, which gives me the
opportunity of splitting my research between Karolinska Institutet
(Stockholm, Sweden) and National Institute of Health (Bethesda, USA).
The main goal of my research is to increase our understanding of the cellular
and synaptic mechanisms underlying neuronal synchronization and electrical
oscillations in neuronal networks during physiological and pathological
states. This knowledge is essential to elucidate pathological network
changes, a crucial step to finding new ways of rescuing altered brain
oscillations and defining new targets for therapeutic intervention. We use
ex-vivo electrophysiology, imaging, and network modeling to investigate gamma
frequency oscillations in the neuronal networks of the hippocampus, which
plays an important role in higher brain functions that are affected in
various brain disorders.

The guiding thread of my research is neuronal oscillations, which are
repetitive patterns of neural activity in the central nervous system. The
synchronized activity of large numbers of neurons gives rise
to macroscopic fluctuations of currents, which can be observed in
an electroencephalogram as a rhythmic fluctuation in local field
potentials. The precise timing of neuronal-spike discharges gives rise to the
so-called brain oscillations. Depending on their frequency, oscillations have
been divided into different groups, each of which has been associated with a
specific function.
My project focuses on gamma oscillations, which are characterized by a
frequency range between 30 and 80 Hz. Gamma oscillations can be detected in
multiple brain regions, including the hippocampus where they are the result
of the synchronization of action potentials of excitatory pyramidal cells
(PC) and inhibitory GABAergic interneurons, in particular fast-spiking
interneurons (FSN). Alterations in the synchronous activity of PC and FSN in
the hippocampus are related to cognitive deficits and neurodegenerative
diseases. For this reason, I evaluate the hippocampal network functionality,
which is expressed as gamma oscillations, by performing local field potential
and patch clamp recordings in healthy and pathological acute slices.
The overall aim of my research is to test the hypothesis that rescuing the
early synaptic alterations that trigger gamma oscillations impairment in
multiple neurodegenerative conditions (including after cranial radiotherapy
and Alzheimer’s disease) would prevent the late cognitive decline observed
in these situations. This will provide the basis for a novel approach: detect
and restore the brain oscillatory activity at an early stage to prevent
severe late complications.