Memory impairment is a hallmark of cognitive deficits experienced at some point in life in one-third of our aging population.    Memory impairments can be a comorbidity of neurodegenerative, neuropsychiatric or neurodevelopmental diseases, brain injury, systemic illness, and medication to any of those. They are observed even in the healthy aging population. Hence, there is an urgent need to develop new, reliable strategies and approaches for the treatment of memory deficits. Among all the available approaches, new neurotechnologies based on direct interfacing with the brain using implantable electronic devices for electrical stimulation emerge as promising tools. Direct electrical stimulation in specific brain regions implanted with intracranial electrodes has been successfully used to improve memory functions.  The reproducibility of such positive effects, however, is compromised by limited insight into the underlying physiological mechanisms. Along with new technologies, new target brain sites with a greater potential for modulation of declarative memory functions are being proposed. One of them is the complex of the anterior thalamic nuclei (ATN), a central component of the neural circuit responsible for certain aspects of learning and memory. Damage to either of two brain regions, the medial temporal lobe or the medial diencephalon, is most consistently associated with anterograde amnesia. Within these respective circuits, the hippocampal formation and the ATN (anteromedial, anteroventral, and anterodorsal), but also prefrontal cortex, are the particular structures of interest. In this project, we propose to study the basic electrophysiological mechanisms of electrical ATN stimulation on the physiology of hippocampal and prefrontal circuitry and behavior in freely moving rats. Task 1: First, we propose to test how different stimulating currents (50-500 µA) and stimulation frequencies (3 Hz, 7 Hz, 12 Hz, 50 Hz, 100 Hz, or 150 Hz) applied in ATN affect the physiology of hippocampal and prefrontal neurons and their communication at single-cell and network levels in quiescent states. Task 2: In parallel, we will check how continuous ATN stimulation affects the activity of hippocampal place cells, and prefrontal neurons during a foraging task and quiescent wakefulness, when place cells spontaneously recapitulate past trajectories (replays). We will test six stimulation frequencies at fixed, individually adjusted current intensities. In addition, we will evaluate the network activity and hippocampal-prefrontal neuronal communication. Task 3: Finally, we propose a behavioral task designed to verify if electrical stimulation of ATN at selected current frequencies can improve spatial memory performance. The task is based in an open field arena equipped with a reward dispensing area and nine equally-spaced buttons (3 × 3), which a rat can easily press with a fraction of its body weight. Rats will need to learn and memorize the location and sequence of switches to press at individually-adjusted 50-70% success rate. This will allow us to track both positive and negative changes in spatial memory performance in response to stimulation (the effects can be bidirectional and depend on stimulation current parameters). Between the task sessions, the behavioral apparatus will be transformed into a simple square open field to evaluate how ATN stimulation affects remapping of place fields and firing properties of place cells and prefrontal neurons. We expect the results of this project to advance our understanding of the mechanisms underlying the effects of ATN electrical stimulation and provide stimulation parameters with the highest potential to improve memory performance. The proposed project can directly benefit and be translated into the clinical studies with human patients led by Dr. Michal Kucewicz at the Gdansk University of Technology.