The long-term goal is to understand how the brain learns and remembers. The purpose of learning is informed action: learned facts and events let us use the past to anticipate the outcome of familiar situations. Relevant memories must be available during learning if past events are to inform and be associated with ongoing experience. These abilities require the hippocampus and are devastated in Alzheimer's disease, but their neuronal coding mechanisms are unknown. In an """"""""episodic-like"""""""" memory task, hippocampal activity varied with recent, ongoing, or imminent events when other aspects of behavior were identical, revealing current, prospective, or retrospective coding.
The aim now is to identify firing patterns that predict learning.
Aim 1 will assess hippocampal coding as rats learn new spatial behaviors in a familiar environment. Experiment 1 will oblige rats to make either new or familiar detours before completing a highly familiar, memory-based journey. Because the start and goal of the journeys are unchanged, the same coding of the familiar episodic-like memory structure should be maintained even if detours entail different trajectories. Journey-dependent coding should predict memory performance and rapid learning in novel detours. Experiment 2 will switch the start and goal of journeys in the same environment. Thus the rats will have to learn new journeys in the same spatial environment. Memory performance and journey-dependent coding should decline initially, and the acquisition of journey-dependent, coding should predict performance improvement during learning.
Aim 2 will assess hippocampal coding as rats learn to perform the same memory task but in a new, unfamiliar environment, so the rats will have to learn new spatial representations as well as a new journeys. Journey-dependent and independent coding should be absent initially, but develop rapidly, and the acquisition of journey-related coding should predict performance during learning.
Aim 3 will test if the identified dynamic coding properties appear even when learning is blocked. The same behavioral methods described in Aims 1 and 2 will be used, but one group of rats will be given NMDA receptor antagonists known to impair learning but not memory performance. The strong prediction is that neither stable memory performance nor accompanying hippocampal coding will be affected by the drug, whereas both learning and the dynamic coding properties that accompany it in Aims 1 and 2 will be impaired.
Each aim will include hippocampus-independent tasks that require the same spatial behaviors but not memory, and will assess both population and temporal neural coding. The research should inform the design of rational treatments for amnesia (e.g. by stroke or Alzheimer's disease), including the future development of neural prostheses.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-L (02))
Program Officer
Osborn, Bettina D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
Zip Code
Riceberg, Justin S; Shapiro, Matthew L (2017) Orbitofrontal Cortex Signals Expected Outcomes with Predictive Codes When Stable Contingencies Promote the Integration of Reward History. J Neurosci 37:2010-2021
Seip-Cammack, Katharine M; Young, James J; Young, Megan E et al. (2017) Partial lesion of the nigrostriatal dopamine pathway in rats impairs egocentric learning but not spatial learning or behavioral flexibility. Behav Neurosci 131:135-42
Guise, Kevin G; Shapiro, Matthew L (2017) Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding. Neuron 94:183-192.e8
Shapiro, Matthew (2015) A limited positioning system for memory. Hippocampus 25:690-6
Christoffel, Daniel J; Golden, Sam A; Walsh, Jessica J et al. (2015) Excitatory transmission at thalamo-striatal synapses mediates susceptibility to social stress. Nat Neurosci 18:962-4
Tavares, Rita Morais; Mendelsohn, Avi; Grossman, Yael et al. (2015) A Map for Social Navigation in the Human Brain. Neuron 87:231-43
Seip-Cammack, Katharine M; Shapiro, Matthew L (2014) Behavioral flexibility and response selection are impaired after limited exposure to oxycodone. Learn Mem 21:686-95
Shapiro, Matthew (2013) Spatial navigation: head direction cells are anchored by gravity. Curr Biol 23:R841-3
Riceberg, Justin S; Shapiro, Matthew L (2012) Reward stability determines the contribution of orbitofrontal cortex to adaptive behavior. J Neurosci 32:16402-9
Bahar, Amir S; Shapiro, Matthew L (2012) Remembering to learn: independent place and journey coding mechanisms contribute to memory transfer. J Neurosci 32:2191-203

Showing the most recent 10 out of 27 publications