Persistent Firing, the Entorhinal Cortex, and Neurodegenerative Illnesses

On March 24th, 2020, Carmen Lin (ABD) presented on her study that drew inspiration from the article by Tahvildari et al., “Switching Between ‘On’ and ‘Off’ States of Persistent Activity In Lateral Entorhinal Layer III Neurons.” This article explains how steady activity in the lateral entorhinal cortex (LEC), part of the hippocampal system, allows neurons to encode and maintain information for short-term memory (working memory). Alternating between “on” and “off” states of persistent neuronal activity, which the researchers discovered was capable of being regulated, may be a mechanism to regulate memory function. They were able to induce and terminate persistent firing.

In her research, Lin built on the significance of persistent firing from the layer III of the LEC, suggesting that the persistent firing could be used to help install the conditioned stimulus in mice during trace eyeblink conditioning, which measures associative learning. Through comparing young mice (3-6 months) and aged mice (26-32 months), she found that persistent firing decreased as age increased, but the firing increased as learning increased. Lin explained how this suggested that the firing rate may contribute the memory and learning impairments that the aged mice displayed.

With a new understanding that persistent firing could be controlled and that aging was connected to persistent firing, I wondered if the knowledge could be applied to Alzheimer’s Disease, a seemingly ubiquitous age-related health condition that negatively affects working memory. With the ability to induce and terminate persistent spiking, the function or short-term memory and consolidation of long-term memory could result. Furthermore, the newfound control reminded me of treatments such as Deep Brain Stimulation (DBS), which have shown to be helpful in neurodegenerative illnesses. Perhaps stimulation inspired by the conditions of this study could be utilized in the human brain.

The exciting possibility is also suggested in the article “Memories Retrieved in Mutant ‘Alzheimer’s’ Mice.” Consider an experiment led by the neuroscientist Susumu Tonegawa et al. at Massachusetts Institute of Technology:

 

The researchers engineered the mutant mice to make a light-sensitive protein in neurons in the hippocampus, the part of the brain that encodes short-term memories. Then the scientists placed the mice back into the box, shining a light onto the animals' brains to force the modified neurons to fire. This caused the mice to recall the memory of being shocked, and the animals froze—suggesting that the memory had been encoded in the first place. But the next day, the mice had again forgotten their fear of the box (Reardon). 

Toonegawa et al. found that the stimulation successfully created neural connections between the hippocampus and the LEC. Although the experiment utilized optogenetics, which currently cannot stimulate human brains, Columbia University neurobiologist Christine Denny predicts that “electrical stimulation may succeed where optogenetics has not. Early trials suggest that deep-brain stimulation of the hippocampus prompts the creation of neurons and improves memory in some Alzheimer’s patients” (Reardon). As of now, no one knows how to do so, but given the growth of research surrounding the topic, perhaps a long-lasting treatment for Alzheimer’s is within our reach.

Reardon, Sara. “Memories Retrieved in Mutant ‘Alzheimer's’ Mice.” Scientific American,
Scientific American, 17 Mar. 2016, www.scientificamerican.com/article/memories-retrieved-in-mutant-alzheimer-s-mice/.


Tahvildari, Babak, et al. “Switching between ‘On’ and ‘Off’ States of Persistent Activity in Lateral Entorhinal Layer III Neurons.” Hippocampus, U.S. National Library of Medicine, 2007, www.ncbi.nlm.nih.gov/pubmed/17315198.