Brian Wiltgen

wiltgenEpisodic and contextual memories are encoded within hippocampal and neocortical circuits.  Retrieving these memories is assumed to involve reactivation of neural ensembles that were wired together during learning.  However, this assumption has been difficult to validate.  While it has been possible to follow the activity of individual neurons shortly after learning it has not been possible to examine their activity weeks later during memory retrieval.  In our experiments we are addressing this issue by using transgenic mice to tag activated neurons with a long lasting form of green fluorescent protein (GFP).  In these animals, activation of the c-fos promoter leads to the expression of a histone 2B-GFP (H2B-GFP) fusion protein that is stable for weeks after induction.  Doxycycline administration turns the system off, allowing us to selectively label neurons that were active during learning.

The hippocampus is essential for the storage and retrieval of new episodic memories.  With the passage of time, however, these same memories can be supported by the neocortex without hippocampal involvement.  This process is called systems consolidation and it is thought to occur when the hippocampus reactivates and strengthens neocortical networks after learning.  Although this assumption is widely accepted, there is currently no direct evidence to support it.  To address this significant gap in our knowledge, we are using recently developed genetic tools to: (1) determine if neocortical networks are reactivated after learning, (2) test whether the hippocampus is essential for the replay of recent experiences in the neocortex and (3) determine whether hippocampal activation is sufficient to reactivate neocortical networks that were engaged during learning.  To accomplish these goals, we are combining cellular techniques with the use of new transgenic animals to permanently label neurons that are active during learning.  Tagging these cells allows us to identify networks that encode memory in the hippocampus and neocortex and follow their activity during the consolidation period.  Next, we are using optogentic tools to selectively activate or silence labeled hippocampal neurons and determine the effects on neocortical reactivation.  These strategies will allow us to test assumptions that are central to all major theories of memory consolidation.

Brian Wiltgen is at UC Davis | Lab Website