Harnessing Metaplasticity Through Transcranial Direct Current Stimulation: A Novel Approach to Combat Age-Related Cognitive Decline

Age-related cognitive decline compromises health and independence, largely due to impairments in neural plasticity and memory mechanisms. This project investigates whether transcranial direct current stimulation (tDCS) can fine-tune metaplasticity—an adaptive process that regulates synaptic plasticity thresholds—to preserve memory and enhance cognition in aging brains. We hypothesize that tDCS restores aberrant metaplasticity in aged neural networks, thereby improving synaptic plasticity and associative memory.

Using an optimized Animal Transcranial Electrical Stimulation (tES) system, we will apply precisely controlled tDCS protocols in aged (22–24 months) and young control (2–3 months) rodents. Cognitive outcomes will be evaluated through behavioral tasks, while electrophysiological recordings will assess synaptic plasticity, including mechanisms such as synaptic tagging and capture (STC). Efficacy will be measured at one day, one week, and one month post-stimulation to establish both immediate and sustained effects.

This study leverages existing laboratory infrastructure and collaboration with clinician-scientists specializing in transcranial magnetic stimulation (TMS). Their expertise will help standardize metaplasticity time windows, enhancing translational relevance. Expected outcomes include identifying effective tDCS protocols for restoring metaplasticity and generating mechanistic insights into how neural plasticity can be maintained during aging.

The findings will lay the groundwork for non-invasive interventions against cognitive decline and provide essential preclinical data to support larger collaborative grants and future clinical trials. Ultimately, this project seeks to bridge preclinical discoveries with real-world healthcare solutions, advancing scalable therapies to improve cognitive resilience in aging populations.