Dr. Mark Mayford and his lab have done amazing work illuminating the molecular mechanisms behind learning and memory. Using transgenetic mice, they specifically and acutely label cells involved in memory encoding and synaptic plasticity. In this study, the lab begins to explore the role of the neocortex in the encoding of a memory. They use a c-fos genetic tagging system, optogenetics, and fear condition to observe the specific mechanisms behind encoding of memories in the cortex. They show here that through stimulation of the cortex they can induce context dependent fear conditioned behaviors. When stimulating neural ensembles activated during fear conditioning, fear conditioning behavior could be induced in neutral environment. This stimulation seems to activate downstream cells in the amygdala as well.
To begin in this study, researchers used a fos/tTA-tetO/ChEF-tdTomato bitransgenic system. This allowed them to acutely label cells being activated in the retrosplenial cortex (RSC) during fear conditioning using a controled dox enriched diet to study those specific ensembles of cells. To support this, they showed that activation of these RSC cortex neurons was indeed due to optogenetic stimulation by looking at electrophysiology and channel rhodopsin expression levels. Next, they observed that transgenic mice showed increase in freezing under optogenetic stimulation in a neutral arena compared to wild type mice that received fear conditioning and control groups. This is beginning to show that stimulating the ensemble of cells active during fear conditioning can induce the same behavior even in a different context. Their next experiments try to parse out the different ways these memories may be being encoded in the RSC. Mice were tagged in either Box A or Box B and then shocked in box A. Transgenic mice tagged in Box A and shocked in Box A showed increase freezing over the other groups as shown in the figure below. This displays that the representation of Box A is stable enough to be linked to the shock during subsequent conditioning in Box A. In the final experiment, they go to show that not only does this optogenetic stimulation activate ensembles in the RSC but in downstream cells in the amygdala.
To learn more about Dr. Mayford’s research, please attend his talk on Tuesday, June 5, 2017 at 4pm in the CNCB Marilyn G. Farquhar Seminar Room.
Kevin White is a PhD student currently rotating in Dr. Axel Nimmerjan’s lab in the Biophontonics Center at the Salk Institute.