A circuit for change

February 18, 2014, RIKEN
A circuit for change
Imaging of cell activity (green) across the hippocampus reveals CA2 (red) can detect small changes in a familiar context. Wintzer et al, Journal Of Neuroscience 2014. Credit: RIKEN

To answer the seemingly simple question "Have I been here before?" we must use our memories of previous experiences to determine if our current location is familiar or novel. In a new study published in the Journal of Neuroscience researchers from the RIKEN Brain Science Institute have identified a region of the hippocampus, called CA2, which is sensitive to even small changes in a familiar context. The results provide the first clue to the contributions of CA2 to memory and may help shed light on why this area is often found to be abnormal in the schizophrenic brain.

Change comes in many flavors; if we move to a new country, city or house it is easy to recognize the novelty of the environment, but if we come home to find the furniture rearranged or a new piece of art on the wall, this recognition may be much slower. Scientists believe this is because memory formation requires comparing current information with previous experience and the larger the overlap, the more difficult the distinction. It has long been known that the hippocampus is a region of the brain crucial for this type of memory, however the identification of neurons responsible for this comparison has remained elusive.

In this study Marie Wintzer, Roman Boehringer, Denis Polygalov and Thomas McHugh used genetically modified mice and advanced cell imaging techniques to demonstrate that while the entire is capable of detecting large changes in context, the small and often overlooked CA2 region is exquisitely sensitive to small changes.

Mice were familiarized with one context and then placed either in a much different context or back in the original with small alterations, such as several new small objects. By detecting the expression of activity induced genes Wintzer and colleagues were able to demonstrate that just a few new objects in the otherwise unchanged context completely altered the pattern of active cells specifically in CA2. Mice that had been genetically engineered to lack this CA2 response explored the new context much less than their normal siblings.

A circuit for change
Imaging of cell activity (green) across the hippocampus reveals CA2 (red) can detect small changes in a familiar context. Wintzer et al. Journal Of Neuroscience 2014. Credit: RIKEN

"CA2 has often been overlooked or simply grouped together with its more prominent neighbors, but these data suggest it's unique and important for recognizing and reacting to changes in our environments" explains Dr. McHugh, the leader of the study.

Compared to rodents, human CA2 is proportionally larger, but still as mysterious. One intriguing finding has been that early in the onset of schizophrenia and bipolar disorder there is a loss of inhibitory neurons specifically in CA2. In addition to the memory problems that accompany these diseases, patients often exhibit a hyper-sensitivity to changes in environment and routine. This study suggests there may be a functional relationship between this sensitivity and CA2 dysfunction, hinting at a new circuit to target in our attempts to understand the function of both the normal and diseased brain.

Explore further: Novel combination of techniques reveals new details about the neuronal networks for memory

More information: Marie E. Wintzer, Roman Boehringer, Denis Polygalov, Thomas J. McHugh (2014). The hippocampal CA2 ensemble is sensitive to contextual change. J. Neuroscience, 2014.

Related Stories

Novel combination of techniques reveals new details about the neuronal networks for memory

February 7, 2014
Learning and memory are believed to occur as a result of the strengthening of synaptic connections among neurons in a brain structure called the hippocampus. The hippocampus consists of five subregions, and a circuit formed ...

Immunity restrained by ion influx

July 22, 2011
B cells maintain stockpiles of calcium ions (Ca2+), which are released during the course of the immune response. When the presence of a foreign antigen stimulates the B cell receptor (BCR) complex, these internal reserves ...

The pauses that refresh the memory

November 29, 2013
Sufferers of schizophrenia experience a broad gamut of symptoms, including hallucinations and delusions as well as disorientation and problems with learning and memory. This diversity of neurological deficits has made schizophrenia ...

Study reveals how the brain links memories of sequential events

January 23, 2014
Suppose you heard the sound of skidding tires, followed by a car crash. The next time you heard such a skid, you might cringe in fear, expecting a crash to follow—suggesting that somehow, your brain had linked those two ...

Modifying activity of neuronal networks that encode spatial memories leads to formation of incorrect fear memory in mice

September 13, 2013
The formation and retrieval of memories allows all kinds of organisms, including humans, to learn and thrive in their environment. Yet our memories are not always accurate, and mistaken remembrances can have important consequences, ...

Recommended for you

Your brain responses to music reveal if you're a musician or not

January 23, 2018
How your brain responds to music listening can reveal whether you have received musical training, according to new Nordic research conducted in Finland (University of Jyväskylä and AMI Center) and Denmark (Aarhus University).

New neuron-like cells allow investigation into synthesis of vital cellular components

January 22, 2018
Neuron-like cells created from a readily available cell line have allowed researchers to investigate how the human brain makes a metabolic building block essential for the survival of all living organisms. A team led by researchers ...

Finding unravels nature of cognitive inflexibility in fragile X syndrome

January 22, 2018
Mice with the genetic defect that causes fragile X syndrome (FXS) learn and remember normally, but show an inability to learn new information that contradicts what they initially learned, shows a new study by a team of neuroscientists. ...

Epilepsy linked to brain volume and thickness differences

January 22, 2018
Epilepsy is associated with thickness and volume differences in the grey matter of several brain regions, according to new research led by UCL and the Keck School of Medicine of USC.

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.