Do You Remember? Life Without a Hippocampus (by Danielle Steinbach)
Apr 01, 2026
Many people think of brain surgery as a highly modern affair that has really only become particularly trustworthy in the late twentieth century. Certainly, there was much more risk for patients going under for brain surgery in the 1950s than there is now in 2026. Indeed, the number of surgeries that occur on a yearly basis has multiplied rapidly since the turn of the 21st century.
However, despite the extraordinary risk involved, every once in a while there was a case in the 1900s that was so bleak and devastating that patients would opt to take the gamble of undergoing crude forms of neurosurgery. Henry Molaison was such a case.
In the years leading up to a momentous surgery in 1953, Molaison suffered with severe seizures that impacted the quality of his life enough for him to consider drastic methods like the one proposed by William Scoville. Scoville was a visionary in the field with a bold personality and uncommon courage, but perhaps that’s a given for anyone who was bold enough to make a career out of neurosurgery the way it was back in the 1950s.
When presented a patient with epilepsy, the more conservative physician in the mid-twentieth century may have prescribed anti-seizure medications such as phenobarbital. But the rarest physician like Scoville saw patients like Henry Molaison and took it upon himself to completely excise the parts of his brain that he theorized to be the origin of the seizures.
The day of his surgery, Henry Molaison woke up with a brain overcome by aberrant, sporadic surges of electrical activity. The day after, he woke up with most of his hippocampus and amygdala gone.
From previous blogs and your own reading, you may know the importance of the hippocampus in memory, and so you may think that Henry Molaison must have become a complete amnesiac after his surgery. However, this was in fact not the case. Henry Molaison suffered from a very specific type of amnesia called anterograde amnesia. That is, he could recall events from his past–he knew who his parents were, where he grew up, and could have named his best friends from school. What he could not do is form new memories after his surgery.
Why?
Because the hippocampus is responsible for encoding memories into long-term storage, but not necessarily for storing those memories once they are encoded elsewhere in the cerebral cortex. Thus, excising the majority of Henry’s hippocampus led to an inability to encode new memories into long-term but his understanding of his past life–information that was stored in connections dispersed throughout his cerebral cortex–was safe.
Henry Molaison’s case served as an impetus to researchers around the world to break deeper into the understanding of memory. It is a truly extraordinary capability of human beings to effortlessly store so many decades of information in their brains. It’s an ability we often take for granted too.
As is the case with anything concerning the architecture of the brain, there exists an extremely fine cascade of events in the genome, the epigenome, and the proteome that support the construction of the hippocampus as a fetus develops and after birth. I’d like to take us through a brief summary of those hard-coded molecular sequences now.
The Genetics of Memory
We will begin with the emergence of the nervous system in a fetus. There exist so far three vesicles that arise from the ectoderm, the outermost of three tissue (or “germ”) layers that have developed in the fetus. Those three vesicles which are destined to become the forebrain, midbrain, and hindbrain respectively will then further split into more specialized regions. The part of the ectoderm we will focus on now is called the dorsomedial telencephalon, an outgrowth from the anterior bulge (the prosencephalon).
It is from the dorsomedial telencephalon that the hippocampus will emerge and the fetus will eventually be equipped with the ability to remember events that will occur over the next eighty years.
With enough cells amassed in the telencephalon for rapid differentiation and structuring to commence, the Wnt genetic signaling pathway will upregulate the activity of numerous genetic pathways involved in neuronal differentiation. Proteins that trigger downstream Wnt signaling cascades bind to cells in the telencephalon expressing FZD1 receptors, leading to the activation of Frizzled proteins that then increase transcription of neuronal differentiation genes.
In addition to the Wnt pathway, the Lhx2 and Lhx5 genes are responsible for the production of LIM homeobox transcription factors, critical proteins in guiding the overall structural development of the hippocampus. Mice knockout studies have also implicated the Nr2f gene family in hippocampal cell development, although the specific mechanisms through which they play this role remains a topic of investigation.
The study of memory is ongoing and–in all likelihood–the entire mystery of how memory works will not be solved in either of our lifetimes. Case studies of patients such as H.M. and knockout experiments with various candidate genes have allowed for a lot of ground to be broken in the investigation of the hippocampus.
If we understand the basis of memory, we can understand how to reverse the declines in memory that occur in millions of adults over decades. The ability to restore that–the memories of one's life and loved ones–would be one of the greatest gifts of medicine.
-- Danielle Steinbach
Sources
https://thejns.org/view/journals/j-neurosurg/137/3/article-p886.xml
https://news.mit.edu/2013/suzanne-corkin-permanent-present-tense-0514
https://www.sciencedirect.com/science/article/pii/S0301008224000352
https://www.ncbi.nlm.nih.gov/books/NBK557414/#:~:text=Structure%20and%20Function,%5D%5B5%5D%5B6%5D