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Research

The Burwell Laboratory studies the structure and function of the cortical regions that surround the hippocampus. In primates this system is referred to as the medial temporal lobe (MTL). In rats, we prefer to use the term hippocampal_system (HS) because the cortex of the rat brain is smooth and is not divided into discrete lobes. The HS consists of several interconnected structures, including the hippocampal_formation (the dentate gyrus, fields CA3, CA2, and CA1, and the subiculum) and the parahippocampal_region (perirhinal (PER), postrhinal(POR)/ parahippocampal, and entorhinal cortices, the pre- and parasubiculum). These regions exhibit substantial cellular, structural, and connectional homology across rodent and primate brains. Because of this homology, we think that rodents provide an excellent animal model of human MTL function and the neural bases of memory.

Funding

  • National Science Foundation (NSF) Award: Cognitive Functions of the Postrhinal Cortex (07/2005-06/2010). PI: Burwell
  • NSF EFRI Award (EFRI 0937848) Dynamic Sensing and Actuating of Sensory and Motor Neural Microcircuits, 2009-2013, PI: Arto Nurmikko, Co-PI: Burwell.
  • DARPA: Brain Reorganization and Plasticity to Accelerate Injury Recovery: Multi-scale and Multi-modal Models Enabled by Next Generation Neurotechnology, 09/2010-08/2014, Stanford PI: Krishna Shenoy, Brown PI: Arto Nurmikko, Co-PI: Burwell.

 

Methods

Here at the Burwell lab, we are especially interested in how visual and spatial information guide behavior in rats. We recently developed a novel apparatus in which we back project visual stimuli to the floor of an exploratory field. This Floor_Projection_Maze allows us to automate the visual appearance of the floor of the maze. We have found that rats readily learn about the visual appearance of the floors. For examples, see these movies of rats performing difficult two-dimensional object discriminations*, a contrast_sensitivity* task, and navigation* using landmarks. This powerful new tool is allowing us to address questions about hippocampal system function in novel ways.

Our current work addresses functions of hippocampal and parahippocampal using in vivo electrophysiology in behaving rats. We have two, 32-channel Plexon MAP data acquisition systems interfaced with CinePlex tracking systems and MedAssociates behavioral control systems. Using stereotrode_and_tetrode recording methods in behaving rats, we are able to examine neuronal_correlates of behavior in the perirhinal and postrhinal cortices and compare those correlates with the related hippocampus and entorhinal cortex.

Much of our earlier work employed permanent lesion techniques. We are currently developing new methods that will allow us to use optogenic_techniques to transiently excite or inactivate the perirhinal or postrhinal cortices.

* links to videos in WMV format. If you have trouble viewing the videos, please try viewing them in Internet Explorer.

Questions of Interest

1) How and where is context encoded in the brain?

We are currently addressing questions about how individual stimuli and spatial context are encoded in the brain and how representations of context interact with other items in memory. We know from prior studies (see publications) that both perirhinal and postrhinal cortices are necessary for processing contextual information, but it is not clear how each region contributes. One approach we are using is a biconditional_discrimination_task in the Floor Projection Maze in which the background context determines which object is correct.

2) Do the perirhinal and postrhinal cortices work together to link objects to places?

Current thinking suggests that the postrhinal cortex processes visual and spatial information and the perirhinal cortex processes information about discrete stimuli or objects. Yet, there are strong connections between the two regions. We think that the connections between the two regions may support representations that link objects to place. Current work is addressing this hypothesis.

3) How and where are landmarks encoded, and how are they used to guide navigation?

We have developed a novel navigation task, the terrain location association (TLA) task, that permits assessing how landmarks guide behavior in spatial tasks. The new task employs the Rear Projection Maze in order to back project digital image “terrains” to the maze floor. We are able to track spatial behavior (Plexon Cineplex) and neuronal activity (Plexon MAP System) during performance on the task. Once rats have become familiar with the standard terrain, they can be tested on various geometric transformations in the Rear Projection Maze.

4) Do parahippocampal structures have attentional functions?

The 5 Choice Serial Reaction Time Task (5CSRT), developed by Trevor Robbins at Cambridge University, tests specific types of attention, including sustained, divided, and selective attention. In the classic task, rats are placed in an operant chamber with a wall that has five nosepoke holes with stimulus lights inside. The rat must detect a light stimulus that appears randomly in one of the five nosepoke holes. We are currently developing a version of this task for the Floor Projection Maze so that we can have more control over visual distractors. This approach will allows us to use electrophysiological and optogenetic techniques to directly measure the role of the perirhinal and postrhinal cortices during performance on this task.

5) How does the prefrontal cortex interact with parahippocampal system structures to guide memory?

One interest in the lab is how interactions between prefrontal cortex and hippocampal system structures interact in the service of memory. We are currently developing a task shifting task in the Rear Projection Maze that is analogous to task_shifting tasks used in humans. Our plan is to investigate prefrontal-hippocampal interactions using optogenetic techniques and single unit recording in behaving rats on this novel task.