UCLA Scientists use Stereo Investigator to Quantify Juvenile Neurogenesis in Mice

In the period of juvenile life, between birth and adulthood, a mouse brain adds a significant number of new neurons; nearly doubling their number in some regions. Researchers at the University of California Los Angeles published their findings last week in Frontiers in Behavioral Neuroscience.  Their findings showed that these new neurons may aid in the development of several cognitive skills.

 

Using a transgenic mouse model that lacked the ability to make new neurons after birth, the way a normal mouse does, the researchers were able to quantify the number of neurons contributed to the brain by postnatal, juvenile, and adult neurogenesis.

 

At age intervals between 14 days and 24 months, the researchers used the optical fractionator probe in Stereo Investigator to estimate cell numbers in the regions of the brain where new neurons are known to be continuously generated after birth. Their results show that during juvenile life parts of the olfactory bulb increase in cell number by 40%, while parts of the hippocampus, a brain structure known to be important in short term memory, grew by 25%. Additionally, in parts of the brain where no postnatal neurogenesis is known to occur cell numbers decreased significantly during this same period of life in all the mice tested.

 

MBF Staff Scientist Dr. Jose Maldonado, who is a co-author of the study, spoke to us about his methods: “Using Stereo Investigator I was able to quantify cells with high enough precision that we were able to clearly see changes in cell numbers (both up and down) in different parts of the mouse brain across the life of the animal. These cell number estimates describe the dynamic nature of cell numbers in the postnatal brain— in some areas neurons are added and in some they are lost. This shows that the brain of mice and perhaps other mammals is not really ‘done’ being built until the organism is in adulthood.”

 

The researchers administered behavioral tests dealing with sound, smell, fear, and new environments to see how the mouse’s ability to learn and adapt to its environment may have changed due to the inability to add postnatally generated neurons.

 

According to the study’s co-author Dr. Jesse Cushman, several cognitive deficits were observed in mice where juvenile neurogenesis was prevented, and males and females were affected differently. Not surprisingly they found the importance of smell in learning reduced in the transgenic mice, and transgenic male mice were unable to remember new environments. Additionally, mice lacking juvenile neurogenesis who were trained to be afraid of a particular sound were excessively afraid of new sounds—a behavior observed in people with anxiety disorders.  Dr. Cushman explained that we see this behavior, “particularly in post-traumatic stress disorder, where for example, any loud sound may trigger an excessive fear response once a soldier returns home to civilian life,” he said.

 

Read the full paper in Frontiers in Behavioral Neuroscience.

 

Reference

Cushman JD, Maldonado J, Kwon EE, Garcia AD, Fan G, Imura T, Sofroniew MV and Fanselow MS (2012) Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories. Front. Behav. Neurosci. 6:3. doi: 10.3389/fnbeh.2012.00003