Name of Fellow

    Dr Francesco Tamagini



    Alzheimer's Society

    Contact information of fellow


    United Kingdom

    Title of project/programme

    Progressive functional disruption of inhibitory neurons in tauopathy

    Source of funding information

    Alzheimer's Society

    Total sum awarded (Euro)

    € 267,981

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Alzheimer's disease & other dementias


    Research Abstract

    Tauopathy is a canonical pathological feature of multiple forms of dementia including Alzheimer’s disease (AD). Tauopathy is thought to disturb the function of CNS circuits and lead to neurodegenerative processes. To date, practically all experimental work examining circuit function in laboratory models of tauoapthy has focussed on the excitatory glutamatergic synapse. My own recent work in models of AD-related amyloidopathy, however, has uncovered neurophysiological deficits in inhibitory neurons. In this fellowship I propose to use a well-established murine model to address how hippocampal inhibitory synaptic function is modified by progressive tauopathy. A key motivation for these studies is observations recently made in my host groups that are suggestive of dysregulated synaptic inhibition in these same mice. I propose to combine neurophysiology, neuroanatomy and in vivo imaging to address inhibitory neuron properties. Neurophysiologically, I will study the properties of inhibitory cells using brain slices obtained from mice at 4 different pathological stages. I will look at excitatory drive to hippocampal interneurons, their intrinsic excitability properties and their GABAergic output to pyramidal cells. By filling the cells during these recording and then reconstructing their architecture I will also examine how the neuroanatomy of GABAergic cells is impacted by tauopathy. Finally, I will look at GABAergic cell activity within intact networks in vivo using 2-photon imaging of stratum oriens cells virally expressing the genetically-encoded Ca2+ indicator GCaMP6. Together these data will provide the first wide-reaching assessment of inhibitory synaptic function in tauopathy, and may point to new potential for therapeutic avenues for AD.

Types: Fellowships
Member States: United Kingdom
Diseases: Alzheimer's disease & other dementias
Years: 2016
Database Categories: N/A
Database Tags: N/A

Export as PDF