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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive March 3, 2014

 

The hippocampus is a pair of seahorse-shaped structures in the brain's temporal lobes.
  It plays a critical role in our ability to remember the who, what, where, and when
of our daily lives.

Image Credit: WikiMedia.org






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Pinpointing area of social memory

Researchers have determined that a small region of the hippocampus - known as CA2 - is essential for social memory, the ability of an animal to recognize another of the same species.

A better grasp of the function of CA2 could prove useful in understanding and treating disorders characterized by altered social behaviors, such as autism, schizophrenia, and bipolar disorder.

The findings were made in mice and are published in the online edition of Nature.

Scientists have long understood that the hippocampus—a pair of seahorse-shaped structures in the brain's temporal lobes—plays a critical role in our ability to remember the who, what, where, and when of our daily lives.


Recent studies have shown that different subregions of the hippocampus have different functions:

the Dentate Gyrus is critical for distinguishing between similar environments

the CA3 enables us to recall a memory from partial cues (e.g., Proust's famous madeleine)

the CA1 region is critical for all forms of memory


"However, the role of CA2, a relatively small region of the hippocampus sandwiched between CA3 and CA1, has remained unknown," said senior author Steven A. Siegelbaum, PhD, professor of neuroscience and pharmacology, chair of the Department of Neuroscience, a member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, and a Howard Hughes Medical Institute Investigator.

A few studies have suggested that CA2 might be involved in social memory, as this region has a high level of expression of a receptor for vasopressin, a hormone linked to sexual motivation, bonding, and other social behaviors.

To learn more about this part of the hippocampus, researchers created a transgenic mouse in which CA2 neurons could be selectively inhibited in adult animals. Once the neurons were inhibited, the mice were given a series of behavioral tests.


"The mice looked quite normal until we looked at social memory. Normally, mice are naturally curious about a mouse they've never met; they spend more time investigating an unfamiliar mouse than a familiar one. In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory."

Frederick L. Hitti, MD-PhD student in Dr. Siegelbaum's laboratory, who developed the transgenic mouse, and first author.


In two separate novel-object recognition tests, the CA2-deficient mice showed a normal preference for an object they had not previously encountered, showing that the mice had an interest in novelty. In another experiment, the researchers tested whether the animals' inability to form social memories might have to do with deficits in their sense of smell — crucial to normal social interaction. However, the mice had no loss in ability to discriminate social or non-social odors.

In humans, the importance of the hippocampus for social memory was famously illustrated by the case of Henry Molaison, who had much of his hippocampus removed by surgeons in 1953 in an attempt to cure severe epilepsy. Molaison (often referred to as HM in the scientific literature) was subsequently unable to form new memories of people. Scientists have observed that lesions limited to the hippocampus also impair social memory in both rodents and humans.


"Because several neuropsychiatric disorders are associated with altered social behaviors, our findings raise the possibility that CA2 dysfunction may contribute to these behavioral changes."

Steven A. Siegelbaum, PhD, professor of neuroscience and pharmacology, chair of the Department of Neuroscience, member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, and a Howard Hughes Medical Institute Investigator.


This possibility is supported by findings of a decrease in number of CA2 inhibitory neurons in people with schizophrenia and bipolar disorder, as well as altered vasopressin signaling in autism.

Therefore, CA2 may provide a new target for therapeutic approaches to the treatment of social disorders.

Abstract
The hippocampus is critical for encoding declarative memory, our repository of knowledge of who, what, where and when1. Mnemonic information is processed in the hippocampus through several parallel routes involving distinct subregions. In the classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to dentate gyrus to CA3 and then to CA1, the main hippocampal output2. Genetic lesions of EC (ref. 3) and hippocampal dentate gyrus (ref. 4), CA3 (ref. 5) and CA1 (ref. 6) regions have revealed their distinct functions in learning and memory. In contrast, little is known about the role of CA2, a relatively small area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic circuit linking EC input with CA1 output7. Here we report a novel transgenic mouse line that enabled us to selectively examine the synaptic connections and behavioural role of the CA2 region in adult mice. Genetically targeted inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory—the ability of an animal to remember a conspecific—with no change in sociability or several other hippocampus-dependent behaviours, including spatial and contextual memory. These behavioural and anatomical results thus reveal CA2 as a critical hub of sociocognitive memory processing.

Authors
Frederick L. Hitti & Steven A. Siegelbaum

Nature (2014) doi:10.1038/nature13028
Received 05 December 2013 Accepted 10 January 2014 Published online 23 February 2014  The paper is titled: "The hippocampal CA2 region is essential for social memory."

The study was supported by a Ruth L. Kirschstein F30 National Research Service Award from the National Institute of Mental Health and the Howard Hughes Medical Institute.

The authors declare no financial or other conflicts of interests.

Columbia University's Mortimer B. Zuckerman Mind Brain Behavior Institute is an interdisciplinary hub for scholars across the university, created on a scope and scale to explore the human brain and behavior at levels of inquiry from cells to society. The institute's leadership, which includes two Nobel Prize-winning neuroscientists, and many of its principal investigators will be based at the 450,000-square-foot Jerome L. Greene Science Center, now rising on the university's new Manhattanville campus. In combining Columbia's preeminence in neuroscience with its strengths in the biological and physical sciences, social sciences, arts, and humanities, the institute provides a common intellectual forum for research communities from Columbia University Medical Center, the Faculty of Arts and Sciences, the School of Engineering and Applied Science, and professional schools on both the Morningside Heights and Washington Heights campuses. Their collective mission is to further our understanding of the human condition and to find cures for disease.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.