Resources
Authors & Affiliations
Isaac Grennan, Brook A L Perry, Anna Verghese, Melissa Jones, Oliver Harmson, Colin G McNamara, Robert Toth, Joram van Rheede, Andrew Sharott
Abstract
Deep brain stimulation (DBS) of the fornix is currently being trialled in the treatment of memory impairment, including in Alzheimer’s disease. Commonly, DBS is delivered continuously at 130Hz, but the effect on memory performance of such stimulation has been mixed. Clinicians have suggested that delivering stimulation timed to ongoing neural activity may enhance the efficacy of DBS. Theta oscillations in the hippocampus, which have been hypothesised to support learning and memory, may provide a read out of memory relevant neural activity. Supporting this, optogenetic stimulation of the hippocampus locked to certain phases of theta oscillations has been found to enhance memory performance. Given that the fornix contains both hippocampal afferents and efferents, we hypothesised that fornix DBS may allow us to modulate hippocampal activity, more translationally than using optogenetic stimulation. Using tetrode recordings in rats running on a linear track, we investigated the effects of theta-locked fornix DBS on hippocampal physiology. Single electrical pulses evoked diverse responses in hippocampal single units in both putative pyramidal cells and interneurons. We verified that we were able to accurately deliver fornix DBS locked to specific phases of hippocampal theta oscillations using the Oscilltrack phase tracking algorithm. Theta-locked stimulation modulated the synchronicity of CA1 single units, including the theta-band coherence of spike trains, in a manner that depended on the phase at which fornix stimulation was delivered. These findings suggest that theta-locked fornix DBS can powerfully modulate hippocampal physiology. Future work will probe the effects of theta-locked fornix DBS on memory.