The Days of our Neurons Part III: Hippocampal Neurogenesis

Janani Rajan

Edited by Keshav Ratra

Graphic Designs by Josephine Wang and Olivia Tang

No two people on Earth have led the same life. Every person’s life is enriched with their own individual experiences, which in turn shape their characteristics, values, and personalities. Experiences are a major influence on a person’s character, and these experiences are stored in their memory. Creating memories is one of the major roles of the hippocampus, a complex brain structure in the temporal lobe. The hippocampus stores short-term memory, long-term memory, as well as spatial memory, allowing people to recall these memories as well. However, new memories are formed daily. How does the hippocampus gain the capacity to store new memories everyday?

The process that enables the hippocampus to do this is called neurogenesis, which creates new neurons and neuroglia. Neurogenesis occurs in the developing brain (discussed in The Days of our Neurons Part I: Prenatal Neurogenesis), and in the adult brain in regions such as the olfactory bulb (discussed in The Days of our Neurons Part II: Olfactory Neurogenesis) as well as the hippocampus.

Adult hippocampal neurogenesis occurs in the dentate gyrus of the hippocampus. Even though this is simply referred to as “Hippocampal Neurogenesis”, it is important to note that this occurs only in the dentate gyrus, and not the other subdivisions of the hippocampus. It also generates only one type of neuron, which is the granule cell. Granule cells are relatively small neurons, with small cell bodies. Each one contains about 3-4 short dendrites, and each dendrite contains a claw-like structure at its end. Each granule cell also contains one narrow axon, and in the hippocampus, this axon is glutamatergic. This means that the neurotransmitter glutamate, the primary excitatory neurotransmitter of the nervous system, is stored in its synaptic vesicles and released into neighboring neurons. Granule cells in the dentate gyrus receive excitatory input from the entorhinal cortex, a region of the brain which functions a network of a person’s long-term, short-term, and spatial memories, as well as their perception of time. They send excitatory output to the CA3 region of the hippocampus, a large circuit that stores episodic memories and spatial representations.

Granule cells generated during adulthood start out as stem cells that resemble radial glia, in the dentate gyrus. Radial glia are a set of precursor cells that contribute significantly to prenatal neurogenesis, and these hippocampal precursor cells have similar properties to radial glia. These cells are called RGLs (for radial glia-like cells). RGLs express some of the same biological markers as astrocytes and stem cells, and have the capability to generate neurons and astrocytes only. The cell bodies of these precursor cells are found in the subgranular zone, a thin layer of cells between the hilus (an indentation in the dentate gyrus) and the granule cell layer of the hippocampus. Throughout life, RGLs have the capacity to divide and generate neurons, even during adulthood.

RGL cells quickly multiply, and differentiate into progenitors with glial and neuronal types. These progenitors continue to proliferate, but are capable of dividing and multiplying only a limited number of times. They are also committed to differentiating into either an astrocyte or a neuron.

The neuronal progenitors then enter a stage in which they closely resemble a migratory neuroblast. During this stage, the cells exit the cell cycle and enter a stage of maturation, in which they extend their dendrites and axons. Within a few days after they exit the cell cycle, the neuroblast-like cells extend an axon towards the CA3 region of the hippocampus. Here, they form synapses with clusters of interneurons. These interneurons will serve to regulate the excitatory input and output which will constantly be transmitted through these granule cells as they mature. Similarly, these cells also extend dendrites towards the entorhinal cortex, beginning to create functional connections with the entorhinal cortex as well. This is where the cell begins to make its glutamatergic contact, and will start getting familiar with its function of receiving and transmitting glutamate. There is no set time period for this stage, as the amount of time taken to extend axons and dendrites vary from neuron to neuron. However, once this stage is complete, these neuroblast-like cells will be indistinguishable from older granule cells, and will become granule cells once and for all.

Through this process, approximately 700 new neurons are produced per day in the adult hippocampus. Though this seems like a miniscule number compared to the 86 billion neurons in the entire human body, hippocampal neurogenesis is still integral to the cognitive functions of the brain. The new neurons that are generated through this process are responsible for the formation of new memories, especially memories that involve spatial recognition. In addition to storing new memories and improving memory capacity, new neurons can also improve the quality of these memories, and store the time in which the memory was recorded.

Various studies have shown that increasing hippocampal neurogenesis, or even neurogenesis in general, can decrease symptoms of depression, and improve your overall health. To a certain extent, humans can even control neurogenesis through lifestyle and diet. For example, activities such as learning and exercise increase neurogenesis, while stress and sleep deprivation decreases it. Reducing caloric intake, intermittent fasting, and spacing meals throughout the day can increase neurogenesis, while high saturated fat and increased alcohol intake decrease neurogenesis. It is even scientifically proven that crunchier foods can increase neurogenesis, as they increase mastication, exercising the jaw.

Overall, neurogenesis is a highly significant and intricate process. Neurogenesis can improve our memory formation and mood, reduce stress, and prevent the decline of our bodies as we age. Increased neurogenesis can even help prevent mental health disorders, such as depression. However, we are in control of our neurogenesis, and our body will produce neurons depending on our lifestyle. It is up to us to lead lifestyles that allow higher rates of neurogenesis to occur, for the sake of our health and happiness.

Approved by Dr. Charles Pidgeon.

This blog is protected by US Copyright law and is owned by Dr. Charles Pidgeon.

References:

1. Berg, Daniel A, et al. “Radial Glial Cells in the Adult Dentate Gyrus: What Are They and Where Do They Come from?” F1000Research, F1000 Research Limited, 5 Mar. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC5840617/.

2. Demetre, DC. “What Are Granule Cells?” Sciencebeta, 19 May 2016, sciencebeta.com/granule-cells/

3. Kempermann, Gerd, and Hongjun Song. “Gerd Kempermann.” Cold Spring Harbor Perspectives in Biology, Cold Spring Harbor Lab, 2015, cshperspectives.cshlp.org/content/7/9/a018812.full

4. Cherubini, Enrico, and Richard Miles. “The CA3 Region of the Hippocampus: How Is It? What Is It for? How Does It Do It?” Frontiers in Cellular Neuroscience, Frontiers Media S.A., 5 Feb. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4318343/.

5. Jonas, Peter, and John Lisman. “Structure, Function, and Plasticity of Hippocampal Dentate Gyrus Microcircuits.” Frontiers, Frontiers, 18 Aug. 2014, www.frontiersin.org/articles/10.3389/fncir.2014.00107/full.

6. Thuret, Sandrine. “You Can Grow New Brain Cells. Here's How.” TED, June 2015, www.ted.com/talks/sandrine_thuret_you_can_grow_new_brain_cells_here_s_how.