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Developmental Biology - Hippocampus

Bravery Cells Found In Hippocampus

People are very different when it comes to trying dangerous or exhilarating things...


Why do some people comfortably walk between skyscrapers on a high-wire or raft the Niagara Falls in a wooden barrel whereas others freeze on the mere thought of climbing off escalators in a shopping mall? In a new study, scientists have found that a certain type of cells in the hippocampus play a key role.

People are very different when it comes to trying dangerous or exhilarating things. Even siblings can show dramatic differences in risk-taking behaviour. The neural mechanisms that drive risk-taking behaviour are largely unknown. However, scientists from the Department of Neuroscience of Uppsala University in Sweden and the Brain Institute of the Federal University of Rio Grande do Norte in Brazil have found that some cells in the hippocampus play a key role in risk taking behaviour and anxiety.

In an article published in the journal Nature Communications,the authors show that neurons known as OLM cells, when stimulated, produce a brain rhythm that is present when animals feel safe in a threatening environment (for example, when they are hiding from a predator but aware of the predator's proximity).
The study shows that anxiety and risk-taking behaviour can be controlled by manipulation of OLM cells. Finding a pathway that quickly and robustly modifies risk-taking behaviour is important in treating pathological anxiety. Reduced risk-taking is a trait in people having high anxiety levels.

Adaptive (or normal) anxiety is essential for survival because it protects us from harm. Unfortunately, in a large number of people, anxiety can be dysfunctional and severely interfere with daily life. In these cases, doctors often rely on antidepressants to help patients recover from the dysfunctional state. However, these drugs act in the entire brain and not only in the areas where it is needed and may therefore have severe side-effects.

Controlling anxiety to act in a single brain region and in a very specific group of cells, may be a major breakthrough in treating anxiety and associated disorders like depression. Another interesting finding in the study is that OLM cells can also be controlled by pharmacological agents. In the past, the same group of scientists had found OLM cells are the 'gatekeepers' of memories in the hippocampus and that these cells are very sensitive to nicotine.
'This finding may explain why people binge-smoke when they are anxious'.

Richardson Leao PhD, researcher at the Brain Institute of the Federal University of Rio Grande do Norte.

The participation of the hippocampus in emotions is much less studied than its role in memory and cognition. In 2014, for example, the Nobel prize was awarded for the discovery of "place cells" that represent a biological GPS and underlie the memories of where we are located in our surroundings. In the past decade, scientists have started to appreciate the role of the hippocampus also in regulating emotions.
It is fascinating how different regions of the same brain structure control distinct behaviours and how they interact with each other. Identifying specific circuits that underlie either cognitive or emotional processes is crucial for the general understanding of brain function and for more specific drug development to treat disorders.

Sanja Mikulovic PhD, Developmental Genetics, Department of Neuroscience, Uppsala University, Sweden

The discovery of these neurons and their role in anxiety and risk-taking may open a path for development of highly efficient anxiolytics and antidepressants without common side-effects, such as apathy.

Abstract
Dorsal and ventral hippocampus regions exert cognition and emotion-related functions, respectively. Since both regions display rhythmic activity, specific neural oscillatory pacemakers may underlie their functional dichotomy. Type 1 theta oscillations are independent of cholinergic transmission and are observed in the dorsal hippocampus during movement and exploration. In contrast, type 2 theta depends on acetylcholine and appears when animals are exposed to emotionally laden contexts such as a predator presence. Despite its involvement in emotions, type 2 theta has not been associated with the ventral hippocampus. Here, we show that optogenetic activation of oriens-lacunosum moleculare (OLM) interneurons in the ventral hippocampus drives type 2 theta. Moreover, we found that type 2 theta generation is associated with increased risk-taking behavior in response to predator odor. These results demonstrate that two theta oscillations subtypes originate in the two hippocampal regions that predominantly underlie either cognitive or emotion-related functions.

Authors
Sanja Mikulovic, Carlos Ernesto Restrepo, Samer Siwani, Pavol Bauer, Stefano Pupe, Adriano B. L. Tort, Klas Kullander and Richardson N. Leo.


Acknowledgements
We thank Brian Bland, one of the discoverers of type 2 theta activity, for his insightful comments on a previous version of this manuscript; Stefan Remy for helpful discussions; George Nascimento for technical support; Steven Edwards for help with the CLARITY method; Davi Drieskens for help with illustrations; Cecilia Yates for kindly donating hair from a verified hunter cat; B. Lea and L. Hugo for their continuous motivation. This work was supported by the Kjell and Mrta Beijers Foundation, The Swedish Research Council, the Swedish Brain Foundation, and the Brazilian agency CAPES (CAPES/STINT program). S.M. was supported by SOEB foundation. C.E.R. was supported by SSMF foundation.

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May 6 2019   Fetal Timeline   Maternal Timeline   News  




The hippocampus serves a critical function in memory, navigation, and cognition.
CREDIT: Nature Communications


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