Episodic memories are memories of our personal experiences. These memories are characterized as an ordered series of events that occur in spatial and temporal context. This amazing ability to remember such complex memories enables animals to produce adaptive behavior learned from just single experiences. Devastating diseases, such as Alzheimer’s Disease and Schizophrenia, disrupt the ability to encode and recall episodic memories, and highlight the important need to understand the neurobiological basis of episodic memory.
The research in my lab is aimed towards uncovering the synaptic, cellular and circuit level mechanisms that underlie formation and recall of episodic memory. Furthermore, we aim to understand how these mechanisms become disrupted during neurodegenerative diseases, such as Alzheimer’s Disease. Towards this end, we have developed cutting-edge optical techniques for application in awake-behaving rodents that enable recording and manipulation of neural physiology, from the level of individual synaptic spines up to thousands of simultaneously monitored neurons. These recording techniques are used in combination with virtual reality behavioral paradigms in order to carefully monitor and control animal behavior. In order to make progress towards understanding episodic memory, we focus on neural representations of space and time found in the hippocampus and entorhinal cortex, which are thought to be key components of episodic memories. Together, we use these techniques and approaches in order to answer the following questions:
- What are the principles of synaptic organization and dendritic integration that underlie neural coding of space and time in the hippocampus and entorhinal cortex?
- What synaptic and circuit properties change during learning that underlie encoding of novel neural representations of space and time?
- How are the synaptic and circuit level mechanisms of episodic memory altered in animal models of Alzheimer’s Disease?
University of Wisconsin–Parkside
- Bigus, Erin R and Lee, Hyun-Woo and Shi, Jiani and Heys, James G (2023). Medial entorhinal cortex plays a specialized role in learning of flexible, context-dependent interval timing behavior. bioRxiv, 2023--01.
- Heys JG, Wu Z, Allegra Mascaro AL, Dombeck DA (2019). Inactivation of the Medial Entorhinal Cortex Selectively Disrupts Learning of Interval Timing. Cell Rep, 32(12), 108163.
- Heys JG, Dombeck DA (2018). Evidence for a subcircuit in medial entorhinal cortex representing elapsed time during immobility. Nat Neurosci, 21(11), 1574-1582.
- Heys JG, Shay CF, MacLeod KM, Witter MP, Moss CF, Hasselmo ME (2016). Physiological Properties of Neurons in Bat Entorhinal Cortex Exhibit an Inverse Gradient along the Dorsal-Ventral Axis Compared to Entorhinal Neurons in Rat. J Neurosci, 36(16), 4591-9.
- Heys JG, Rangarajan KV, Dombeck DA (2014). The functional micro-organization of grid cells revealed by cellular-resolution imaging. Neuron, 84(5), 1079-90.
- Heys JG, MacLeod KM, Moss CF, Hasselmo ME (2013). Bat and rat neurons differ in theta-frequency resonance despite similar coding of space. Science, 340(6130), 363-7.
- Heys JG, Hasselmo ME (2012). Neuromodulation of I(h) in layer II medial entorhinal cortex stellate cells: a voltage-clamp study. J Neurosci, 32(26), 9066-72.
- Heys JG, Giocomo LM, Hasselmo ME (2010). Cholinergic modulation of the resonance properties of stellate cells in layer II of medial entorhinal cortex. J Neurophysiol, 104(1), 258-70.
- Issa JB, Tocker G, Hasselmo ME, Heys JG, Dombeck DA (2020). Navigating Through Time: A Spatial Navigation Perspective on How the Brain May Encode Time. [Review]. Annu Rev Neurosci, 43, 73-93.
- Heys JG, Schultheiss NW, Shay CF, Tsuno Y, Hasselmo ME (2012). Effects of acetylcholine on neuronal properties in entorhinal cortex. [Review]. Front Behav Neurosci, 6, 32.
- Barry C, Heys JG, Hasselmo ME (2012). Possible role of acetylcholine in regulating spatial novelty effects on theta rhythm and grid cells. [Review]. Front Neural Circuits, 6, 5.
- Hasselmo ME, Brandon MP, Yoshida M, Giocomo LM, Heys JG, Fransen E, Newman EL, Zilli EA (2009). A phase code for memory could arise from circuit mechanisms in entorhinal cortex. [Review]. Neural Netw, 22(8), 1129-38.