Memory of personal experiences shapes who we are and guides how we behave. As time elapses, we are able to capture the individual moments, group and save them as an interconnected stream of events – a memory episode. In a sense, memory acts like a video recorder. Yet, the neuronal mechanisms that encode and store everyday experience into memory are still largely unknown. The central focus of the Wang Lab is to gain insight into the underlying circuit mechanisms of memory encoding and storage that endow us with the ability to bridge from the past to the future.

Our research primarily concerns a compound brain structure called the hippocampal formation. The hippocampal formation is comprised of the hippocampus and its related brain regions. It plays an essential role in forming memory of everyday experience. In order to understand how the hippocampal circuits implement such functions, it is necessary to first pinpoint how the memory episode is represented in the brain. This can be achieved by identifying the activity traces produced by neurons upon memory activation.

In the hippocampus, neurons preferentially become active as the animal passes through specific locations of an environment. These so-called place cells behave as if the animal remembers those spatial locations. Given that spatial context is an inevitable component of a memory episode, the idea of considering place cells as the generalized neuronal correlates of memory traces has stirred considerable excitement. However, rich sensory cues are present in every environment, which casts doubts on whether place cell activity is simply a manifestation of responsiveness to sensory inputs.

In our lab, we employ memory tasks that manipulate sensory inputs by reversibly toggling the accessible cues on and off. These tasks allow us to isolate the neuronal activity associated with internally stored memories from those attributable to sensory inputs. Since a memory episode is composed of a sequence of interconnected moments instead of unrelated static images, we are particularly interested in the sequential neuronal activity patterns that potentially encode such an episode.

By combining electrophysiological, imaging, and optogenetic approaches with computational modeling, we will seek to understand:

1. How hippocampal circuits generate memory-related sequential activity patterns thus allowing us to remember, think, and plan; and
2. What changes are induced under neurological disease states associated with memory loss, such as Alzheimer diseases.