Restoring hippocampal-cortical circuit and memory dysfunction in prodromal Alzheimer's Disease.

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Brains contain billions of specialised cells, called neurons, which are the fundamental building blocks of every circuit in the nervous system. The principal purpose of a neuron is to transmit information: when they receive sufficient input from other neurons, they send brief electrical pulses, called action potentials, which allows them to communicate with other neurons. Broadly speaking, neurons exist as two types: excitatory neurons, which make other neurons more likely to fire action potentials, and inhibitory interneurons, which make other neurons less likely to fire action potentials. If one were to compare the brain's electrical activity to music, then excitatory neurons provide the notes for the brain's 'music', whilst inhibitory interneurons provide the pauses between notes. All computations in the brain require very precise synchrony between different neurons: without the notes, there would be only silence, and without the pauses, the music would become a cacophony.Recent research has shown that dementias, such as Alzheimer's Disease, cause a dysfunction in inhibitory interneurons. The resulting effects on normal brain function are severe and thought to translate to the cognitive and memory impairments seen in Alzheimer's Disease. Data from our labs shows that selectively manipulating inhibitory interneuron activity can restore normal brain function in mouse models of Alzheimer's Disease. Intriguingly, a similar rescuing effect has recently been attribute to non-invasive light and acoustic stimulation at frequencies similar to the frame rate of video (40 Hz).Our project has two aims. One is of a basic science nature: We would like to determine the mechanisms underlying the rescue effects following stimulation of inhibitory interneurons and delivery of light and acoustic stimuli in mouse models of Alzheimer's Disease. The other aim is of a translational nature: We would like to see whether stimulation of inhibitory interneurons and delivery of light and acoustic stimuli in mouse models of Alzheimer's Disease can actually restore memory function in the early stages of Alzheimer's Disease.