1. The Evolution of Memory:
A Comparison of Adult Hippocampal Neurogenesis Across Primates
Dates of Research Project: May 2016- May 2018
Kleiner, Jamie
404 Westminster Drive Morganville, NJ 07751
(732) 778-5556
Expected Year of Graduation: 2018 CCAS
Majors: Psychology with a concentration in Cognitive Neuroscience, Political Science
Email: JamieKleiner@gwu.edu
GWID: G45739864
Faculty Mentor: Dr. Chet Sherwood
CCAS Professor and Chair of Anthropology

2. Student Project Description
The hippocampus (HP) is a bilateral neuroanatomical structure that is central to the stor-
age and retrieval of long-term memory and spatial navigation. In humans, the HP is an important
structure for episodic memory- autobiographical memories of specific events. While non-human
primates (NHPs) have semantic memory- the ability to remember basic concepts that are not au-
tobiographical, episodic memory is a feature that is unique to humans (Tulving 2002). This form
of memory allows us to distinguish between events that we experience, it also gives us the ability
of foresight to imagine future events (Suddendorf and Corballis 2007). Although the basic struc-
ture of the HP is present in all mammals, there is recent evidence to suggest that the human HP
may have specializations that distinguish it from closely related NHPs in terms of the region’s
relative volume (Barger et. al. 2014) and gene expression (Konopka et. al. 2012). These differ-
ences suggest a linkage between neurobiology and humans’ unique episodic memory. Thus, I
will be studying the neurobiological basis of memory evolution in primates, to better understand
the emergence of episodic memory in humans.
My primary area of focus within the HP is the dentate gyrus (DG) because of its impor-
tant role in controlling the flow of information in the HP. In particular, the DG plays a major role
in the HP’s ability to discriminate similar yet distinct input of events (Teyler and Discenna 1983).
The DG is particularly relevant to this function due to the presence of adult hippocampal neuro-
genesis (AHN)- a process in which new granule cell neurons, referred to as neuroblasts, are cre-
ated (Konefal et. al. 2013). The generation of new neurons is only present in one other region in
the adult mammalian brain, the olfactory bulb.
AHN is present in all adult mammals and is thought to improve the encoding of new
stimuli while preserving previously encoded stimuli (Konefal et. al. 2013). It is argued that AHN
is a mammal-specific feature and that the process provides the DG with enhanced neural plastici-
ty. Yet, there is evidence that indicates considerable variation in the degree of AHN across
species (Amrein et. al. 2011). Quantitative differences in AHN between species might be associ-
ated with variation of neuroplasticity in the DG, which would correlate with differences in the
flexibility of memory among species. Thus, AHN’s role in hippocampal plasticity may be modi-
fied in humans to allow for episodic memory (Kempermann 2012). I therefore hypothesize that
there are quantitative differences in AHN between humans and NHPs. I predict that there is a
greater degree of AHN in humans than in NHPs.
To test this hypothesis, I will quantify and compare AHN in a diversity of primate
species: humans, chimpanzees, bonobos, gorillas, macaques, orangutans, gibbons, baboons,
squirrel monkeys, marmosets, and galagos. Within these species, four individuals will be tested
each. To quantify AHN in the DG, I will focus on two specific layers: the granule cell layer
(GCL) and the subgranular zone (SGZ) (Figure 1). While the GCL and SGZ mostly contain
densely packed mature granule cells, a small proportion of these neurons are newborn neurob-
lasts. All specimens that I will study have previously been sectioned into 40µm-thin sections and
stained by a PhD student, Brian Schilder, in the laboratory where I am conducting this research. I
will identify newborn neuroblasts by studying immunohistochemically stained tissues that have
been labeled for the protein doublecortin (DCX), which is only expressed in neurons undergoing
maturation. The stain causes neuroblasts to be marked with a brown tint, allowing visualization

3. within the two layers (Figure 2). Additionally, the tissue is stained with a standard cresyl violet
stain for Nissl substance to visualize all the cell bodies a blue color. This will allow me to distin-
guish between neuroblasts and mature granule cells (Figure 2). In carrying out this research so
far, I have been using a quantification method called stereology- a method that involves random,
systematic sampling of brain tissue to provide unbiased and quantitative estimates of the number
of cells. This is being performed using a computer program called StereoInvestigator, which is
integrated with a microscope. Essentially, I input specific fields of measurements (such as the
thickness of the tissue and the magnification settings of the microscope) and then quantify cells
with these measures taken into account.
The current project proposal is both an extension and continuation of my research, which
I have been working on since Spring 2016. While I have successfully quantified cells within the
DG of chimpanzees and bonobos, more individuals and species must be compared to infer the
evolution of AHN. I hope to advance my study by quantifying cells within the remaining species
listed above.
I predict there will be a greater percentage of DCX-positive neurons in humans compared
to the NHPs. These results would support the hypothesis that the DG has evolved a higher capac-
ity for neural plasticity in humans through AHN, which allows for our species’ unique ability of
episodic memory. Thus, this study could be a significant contribution to our understanding of the
evolution of human memory.
Figure 1 Dentate gyrus of a marmoset in 4x magnifi-
cation. Outlined in pink is the granule cell layer (GCL)
and outlined in green is the subgranular zone (SGZ).
Figure 2 Dentate gyrus of a chimpanzee in 63x
magnification. The purple surrounding cells are
mature granule cells. The brown cell featured in
the green box is a neuroblast.

4. Student Experience and Goals
Since the end of my sophomore year I have been fortunate enough to be an active partici-
pant in the Laboratory for Evolutionary Neuroscience at The George Washington University’s
(GW) Center for the Advanced Study of Human Paleobiology, headed by Dr. Chet Sherwood.
My work began at the end of last spring and has continued under the supervision of Dr. Sher-
wood and PhD student Brian Schilder. I hope to continue my research for the remainder of my
junior year and throughout Summer 2017. This project proposal is a continuation of my work.
Before working with Dr. Sherwood, I worked at The Social Cognition Laboratory in
GW’s Department of Speech & Hearing, supervised by Dr. Francys Subiaul. This work took
place throughout my freshman year. With Dr. Subiaul, I worked in the Discovery Room of the
Smithsonian Museum of Natural History where we solicited volunteer subjects between the ages
of three to five, at play, to participate in numerous interactive computer games. The goal of this
project was to measure the children’s memory capacity and how their memory influenced learn-
ing outcomes. As a product of my work, I noted positive correlations between older children,
greater memory retention, and improved performance on the given tasks. As a result, working
with Dr. Subiaul sparked my interest in memory and cognition, specifically memory and its in-
fluence on behavior. It was this lab experience that also launched my interest in neuroanatomy. I
began to ask myself - why did memory retention increase with age? How does the brain’s maturi-
ty play a role in long-term memory? What makes humans’ long-term memory distinct from our
closest NHP relatives? It seemed appropriate that my next step was to participate in comparative
neuroanatomical research, in the hopes of answering some of my questions.
During my time in Dr. Sherwood’s lab I have gained considerable experience in compara-
tive neuroscience research. Skills such as learning the proper use of a microscope for stereologi-
cal procedures, discovering different methods of staining tissues, and building a capacity to do
more effective literary research on a highly specific topic are all valuable assets that I am devel-
oping. Dr. Sherwood and Brian have been superbly helpful in advising me on my future career
goals. I have been attending weekly lab meetings and have had the opportunity to learn about
other people’s projects and pursuits. I also have had periodic discussions with Brian based on
literary research that is interesting and relevant to my project. I am excited to be immersed with-
in this lab and hope to continue my work.
I am also happy to be having meaningful discussions with both Brian and Dr. Sherwood
about the other avenues of neuroscience research that I may pursue. For instance, being that I am
a double major in political science and psychology (with a concentration in cognitive neuro-
science), I am exploring avenues where I could meld these two fields together. One specific field
that excites me is neurolaw, a field that focuses on encompassing neurological research pertain-
ing to memory, trauma and addiction within criminal court cases. My project relates to this long-
term goal because I am acquiring the tools necessary to conduct my own research in neu-
roanatomy and memory function. Specifically, memory function is applicable to neurolaw be-
cause of eyewitness reliability and trauma’s impact on memory recall in the courtroom. Thus, I
am beginning to develop an expertise which would be highly valuable in the field of neurolaw.

5. Works Cited
Amrein, I., Isler, K., & Lipp, H. (2011). Comparing adult hippocampal neurogenesis in
mammalian species and orders: Influence of chronological age and life history stage.
European Journal of Neuroscience, 34(6), 978-987. doi:10.1111/j.
1460-9568.2011.07804.x
Barger, N., Hanson, K. L., Teffer, K., Schenker-Ahmed, N. M., & Semendeferi, K. (2014).
Evidence for evolutionary specialization in human limbic structures. Frontiers in Human
Neuroscience Front. Hum. Neurosci., 8. doi:10.3389/fnhum.2014.00277
Kempermann, G. (2012). New neurons for 'survival of the fittest' Nature Reviews Neuroscience.
doi:10.1038/nrn3319
Konefal, S., Elliot, M., & Crespi, B. (2013). The adaptive significance of adult neurogenesis: An
integrative approach. Front. Neuroanat. Frontiers in Neuroanatomy, 7. doi:10.3389/fnana.
2013.00021
Konopka, G., Friedrich, T., Davis-Turak, J., Winden, K., Oldham, M., Gao, F., . . . Geschwind,
D. (2012). Human-Specific Transcriptional Networks in the Brain. Neuron, 75(4),
601-617. doi:10.1016/j.neuron.2012.05.034
Lumsden, C. J., & Wilson, E. O. (1981). Genes, mind, and culture: The coevolutionary process.
Cambridge, MA: Harvard University Press.
Suddendorf, T., & Corballis, M. C. (2007). The evolution of foresight: What is mental time
travel, and is it unique to humans? Behavioral and Brain Sciences, 30(03). doi:10.1017/
s0140525x07001975
Teyler, T. J., & Discenna, P. (1983). The topological anatomy of the hippocampus: A clue to its
function. Brain Research Bulletin, 12(6), 711-719. doi:10.1016/0361-9230(84)90152-7
Tulving, E. (2002). Episodic Memory: From Mind to Brain. Annual Review of Psychology
Annu. Rev. Psychol., 53(1), 1-25. doi:10.1146/annurev.psych.53.100901.135114