Harnessing memory traces for the development of pro-cognitive interventions

Manipulate synaptic plasticity

Resource Mobilisation

Synaptic plasticity changes the firing rate of neurons, which in turn defines the representation of the events we experience around us. A memory trace (or engram) is the cellular representation of these memories. If we can manipulate synaptic plasticity in a way that is specific to a memory (for example a specific melody), we could help the brain to improve learning and to counteract the compromised mobilisation of cognitive resources.

In a recent study, we have found a way to achieve this. We used mild elevations of brain temperature through targeted light delivery to change the firing mode of neurons. When applied to the auditory cortex mice exhibited a strikingly faster learning speed. This research will explore several ways to model and manipulate neuronal firing modes during learning in different species. From this basis, we propose a more general working hypothesis that physical (e.g., tFUS, mid-infrared light, magnetic stimulation of signalling pathways using beads) interventions targeting neuronal plasticity (through direct and cholinergic mechanisms) can promote cognitive function and learning performance. Our investigation of the underlying mechanisms of ultrasound stimulation in the brain, we aim to i) identify mechanosensitive channels and cell-types activated by different regimes of ultrasound stimulation and ii) develop reagents for activation of specific channels/cell-types by subthreshold ultrasound stimulation. In one approach we will use magnetic stimulation of specific synaptic signalling pathways to achieve this (using magnetic beads decorated by antibodies/lectins binding to specific channels, receptors and ECM molecules).