10/17 Han and Yiu

            Han et al. deleted neurons activated during auditory fear memory to attempt to erase the memory. They knew that lateral amygdala (LA) neurons with relatively high CREB levels were preferentially activated during auditory fear memory. They labeled these neurons using HSV vectors in iDTR transgenic mice to elevate CREB levels in small populations of LA neurons. When the CREB-cre vector is injected into the mouse, the stop cassette loxP is excised, and DTR is expressed. When DT is administered, apoptosis occurs. The experiments run by Han et al. show that the cell death of the memory trace erases the fear memory.

            The reserachers proved that the deletion was chronic by testing mice up to twelve days after DT administration. On the twelfth day, the freezing levels were still as low as the second day. Furthermore, these mice were able to relearn the fear memory, which showed that the deletion was not an impairment of overall LA function. However, this made me wonder how many times or how often memory trace neurons could be ablated from the LA without any negative effects for the mouse. Since only a small amount of neurons were recruited and deleted, there were not any negative side effects seen in the mice after one time, but if it was repeatedly done, there may be negative effects. Further experiments could be done to investigate this by subjecting these mice to behavioral tests in the future.

            Yiu et al. sought to determine whether relatively higher LA neuronal excitability before training would preferentially allocate these neurons to a memory trace. They knew from previous research that increased CREB expression caused preferential recruitment on neurons to a fear memory, and ablation of these neurons caused the fear memory to be erased. They aimed to uncover a more detailed reason for the memory erasure. One result of increased CREB in a cell is increased excitability, so the researchers used an extensive amount of techniques to test neuronal excitability. The experiments went beyond using just neuronal excitability by overexpression of CREB; excitability through dnKCNQ2, CNO bound to hM3Dq, and ChR2 were also used. The results were consistent across methods.

            If fear memory deletion was deemed ethical for humans and the technique was safe, it would be difficult to use in a clinical setting. The experiments proved that the vector must be injected before the memory occurs, so it wouldn’t be able to be used to erase a fear memory from a patient’s past. Unless the person knew that they were going to encounter something fearful, then it wouldn’t be useful. If there was a way to inject the vector before fear memory occured, memory deletion could be useful in treating PTSD and other mental illnesses.