Associate Professor Itamar Kahn
The ability to identify minute changes in brain activity that result from the attack of Alzheimer’s disease depends on high-resolution imaging using several modalities (with fMRI being a predominant approach in our lab) complemented by tracking of activity of individual neurons using electrophysiology. Neocortical pyramidal cells are excitatory neurons with long-range axons. As a fundamental computational element of the nervous system, a comprehensive understanding of this class of neurons, including microcircuits molecular specification, behavioral correlates and the effects degenerative processes have on their organization, is necessary if we are to understand and develop therapeutic approaches for Alzheimer’s disease. Current efforts to understand the organization of pyramidal neurons focus on anatomical connectivity using optical and electron microscopy, and functional connectivity using electrophysiology and two-photon microscopy calcium imaging. We complement these efforts by employing in vivo longitudinal brain-wide imaging using fMRI.
In our research, we compare the ability of pyramidal neurons to drive activity at their axonal projection targets by developing methods to measure fMRI signals resulting from single cell activity. We manipulate the integrity of pyramidal neurons (e.g., the disruption they experience in Alzheimer’s disease) using genetic techniques achieving selective impaired cellular physiology. Specifically, we aim to answer the following fundamental questions:
- How do longitudinal progressive changes in cellular integrity, including cell cycle processes, cellular signal transduction, and myelination affect long distance signal transduction at the individual neuron and population levels?
- Would neurodegenerative conditions (and Alzheimer’s disease in particular) differentially affect long-range projection neurons with distinct cortical targets?
- Can we identify functional differences in pyramidal projection neurons by selective functional disruption and relate them to cell subtypes?
The above approach seeks to provide a novel method for dissecting brain-wide connectivity and gain a new understanding of the computational goals of long-distance axonal projections and related cognitive impairments. Furthermore, it seeks to contribute to our understanding of brain-wide structural and functional alterations during the degeneration of brain cells, and potentially reveal novel markers of degeneration that precede the characteristic symptoms of Alzheimer’s disease.