Current Research Projects
Our lab works to understand how neural synchrony shapes information processing, and how that synchrony drives cognitive disorders when it is altered.
The brain depends on precisely timed neuronal activity to control behavior. In the hippocampus, neurons fire in-sync with theta oscillations – rhythmic brain waves occurring at about 5 to 12 times per second — creating windows of time in which neurons can work together to drive cognition. Inhibitory neurons are especially tightly locked to this rhythm, helping route information and keeping excitation and inhibition in balance. However, most of what we know about the function of this precise spike timing comes from correlation, inferred from symptoms of diseases where it breaks down.
Our lab works to directly manipulate neural timing to uncover how small disruptions in spike timing cause cognitive impairment and seizures, and how restoring proper timing can rescue function. Using closed-loop systems, we test how the synchrony of inhibitory neurons shapes plasticity and cognition, both in the healthy brain and in the context of epilepsy and aging.
Strong evidence from the aging field suggests that maintaining hippocampal neural synchrony and excitability into middle age confers resilience against cognitive decline, with the severity of hippocampal deficits correlating with cognitive impairment. Our lab explores this by directly manipulating inhibitory spike timing and determining how cell-network synchrony impacts cognitive decline during physiological aging.
Characterizing cell-network synchrony breakdowns during aging
Using optogenetic tagging strategies, coupled with cognitive batteries, we explore whether inhibitory subtypes lose their spike timing precision during the critical transition to cognitive decline during otherwise healthy aging.
Controlling neural synchrony to aid information processing
We explore whether restoring inhibitory theta phase locking in middle-aged animals will improve hippocampal task performance, while disrupting timing in young adults will accelerate aging-like cognitive impairments.
Theta phase of neural activity can control network reorganization by providing a temporal window for enhanced plasticity — stimulating neuronal activity during one theta phase can facilitate long-term potentiation, while stimulation during the opposite phase can induce long-term depression.
Previously, we developed a tool called PhaSER, which can directly manipulate theta phase locking in real time in awake, behaving animals. This tool uniquely enables bidirectional control of individual neuron spike timing relative to endogenous oscillations while simultaneously monitoring spiking. Our lab uses this tool to explore whether spiking at certain phases of theta may produce beneficial re-organization of the epileptic hippocampal circuit and produce long-lasting, disease-modifying effects.
As our lab continues to grow, we will apply PhaSER in different ways — with the goal of advancing treatment options for people with epilepsy by shedding light on the fundamental mechanisms of hippocampal network dynamics. Three directions are underway:
Freely Moving Behaviors
We're extending PhaSER for use in animals during natural, unrestrained behavior.
PhaSER and Seizures
We're testing whether phase-targeted stimulation can reshape circuit activity during epileptogenesis.
PhaSER and Cognitive Deficits
We're asking whether restoring phase locking can rescue the cognitive deficits associated with epilepsy.
Our lab is interested in identifying how neural synchrony may more universally reflect brain function across health and disease. Current open questions include:
Connectivity
We're performing brain-wide assessments of upstream regions that may show altered connectivity to the hippocampus during physiological aging.
Long-range inhibition
We're interested in how long-range inhibition alters cross-regional communication in epilepsy and aging.
Working memory & attention
We're interested in whether breakdowns in theta phase locking underly the emergence of working memory and attention deficits in aging and disease.
Sex differences
We're exploring sex-specific vulnerabilities to neural synchrony that emerge during aging and in epilepsy.
Neurofeedback
We're interested in whether animals can be trained to spend more time in a state of high phase locking using neurofeedback or sensorimotor training.
Christenson Wick Lab Publications
2025
Interneuron theta phase locking controls seizure susceptibility
bioRxiv, currently under review
2025
Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy
Cell Reports
2023
Progressive Excitability Changes in the Medial Entorhinal Cortex in the 3xTg Mouse Model of Alzheimer's Disease Pathology
Journal of Neuroscience
2023
Chronotate: An open-source tool for manual timestamping and quantification of animal behavior
Neuroscience Letters
Funding and Support
Thanks to these organizations for funding our past and present research
The Simons Foundation
National Institutes of Health (NIH)
The Phil and Penny Knight Campus for Accelerating Scientific Impact
The American Epilepsy Society