Scientists find that associative learning of fear is mediated by a novel dopamine circuit
A team of neurobiologists, led by scientists at the Research Institute of Molecular Pathology (IMP) in Vienna, has identified a novel neuronal circuit in the midbrain that gates fear learning. They found that the neurotransmitter dopamine, so far merely associated with reward and motivation, plays a crucial role in memory formation following aversive events. The study was published online by the journal Nature Neuroscience on 27 June, 2018.
A group of dopamine neurons in the ventral PAG senses aversive events and instructs the amygdala to store these experiences into fear memory
Source: http://connectivity.brain-map.org/projection/experiment/272699357 © 2011, Allen Institute for Brain Science. Allen Mouse Brain Connectivity Atlas. Available from: connectivity.brain-map.org
For any higher organism, it is vital to learn from the past to adapt future behaviors. The formation of fear memories is the prime example in this regard. They help us to associate appropriate defensive behaviors with environmental cues such as sounds and smells that predict previously encountered threats like fights or poisonings. Incorrectly processed fear memories can lead to a variety of fear-related conditions, such as post-traumatic stress disorders.
Animals and humans alike live in complex environments and go through countless experiences, many of them meaningless, and some few of them important. In this setting, the brain has to perform a difficult task: it needs to memorize only the essential associations for later recall, while forgetting the unnecessary rest.
To elucidate the neuronal implementation of this process, Wulf Haubensak, a neuroscientist and Group Leader at the IMP, wondered if dopamine may play an important role. A widely known hormone for motivation and happiness, it seemed a rather unlikely candidate, at first. However, dopamine has some interesting properties. It is released following important events - such as getting a reward - and thus might act as a signal to memorize such experiences.
Haubensak and his group teamed up with physiologist Volkmar Leßmann and colleagues at the Otto-von-Guericke University in Magdeburg to explore this in animal models. The team conditioned mice to learn that an acoustic signal - the environmental cue - predicts a mild foot shock representing the threat. Using advanced technology such as live calcium-imaging and optogenetics, the scientists were able to track and manipulate specific subsets of neurons in the brain during the learning task.
In particular, they found a specific set of neurons in the midbrain called the ventral periaqueductal grey (vPAG). Intriguingly, these neurons become active when the animal begins to learn to associate the cue with the aversive shock - that is, during subjectively important events for the animal.
When activated, they release dopamine and instruct the amygdala - a major emotion center in the brain - to associate the tone with the shock and store this experience into synaptic long-term memory. In the experiments, temporally inactivating this connection during fear memory tasks resulted in mice that were no longer able to remember previous fearful experiences, while over-activation lead to excessive memories that would normally be suppressed.
The discovery of the link between these relatively unknown dopamine neurons in the ventral PAG and the amygdala was key to connecting the dopamine-system to fear memory formation. “This finding adds a completely different angle to dopamine neurons, widely regarded as responsible for reward and motivation only”, says Florian Grössl, first author of the publication and a Postdoc in the Haubensak-lab.
“Our study shows that they direct fear memory formation and reveals a new dopaminergic circuit module between the PAG and the amygdala that is crucial for emotion processing: it filters out important experiences and stores them into associative memory.”
In humans, dopamine neurons originating from the PAG-region are wired in a very similar way as in mice. They are involved in pain processing and have recently been shown to also play a role in memory formation. Following the discovery by the Haubensak-team, it would be important to investigate if dysregulation of ventral PAG dopamine neurons could lead to psychiatric disorders. They might also provide a clue to side effects observed in patients that are treated with medication affecting the dopamine system, as in Parkinson’s disease and addiction disorders.
Original publication https://www.nature.com/articles/s41593-018-0174-5
Grössl et al.: Dorsal tegmental dopamine neurons gate associative learning of fear. Nature Neuroscience, 27 June, 2018. DOI: 10.1038/s41593-018-0174-5
About the IMP
The Research Institute of Molecular Pathology (IMP) in Vienna pursues world-class research in basic molecular biology. It is located at the Vienna BioCenter and largely sponsored by Boehringer Ingelheim. With over 200 scientists from 40 countries, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. http://www.imp.ac.at
http://www.imp.ac.at/supplements - An illustration can be downloaded from the IMP website
Katharina Vorwerk | idw - Informationsdienst Wissenschaft
Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern
Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz
DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.
The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...
Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.
The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...
Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.
Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.
"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
22.03.2019 | Life Sciences
22.03.2019 | Life Sciences
22.03.2019 | Information Technology