Astrocytic mors of the hippocampus responsible for the conditioned place preference

If anyone asks me "are you addicted to coffee?" I can say, "Yes, it seems to be, but only on the condition, only in my office." I did not really want coffee at home, but being in the office, where I was drinking coffee all the time in search of the nervousness of caffeine, seemed to trigger my brain depending on caffeine. It is often said that breaking one's bad habits or additions is a matter of will. However, as explained Bruce Alexander, a researcher in the field of behavioral research, "Addiction is an adaptation." It's not you, it's the cage in which you live." (Source: Chasing the Scream: The first and last days of the war on drugs). Studies have revealed that environmental stimuli such as places are the main force of our addiction. For example, studies of veterans of the heroin-dependent Vietnam War revealed that changes in their place of life – returning home from the battlefield were the hidden strength to break their dependency on the drug so effectively.

When you feel happy or pleasant, several areas of the brain participate to feel, memorize and repeat the action. Specifically, the hippocampus is responsible for the acquisition of spatial memory. People can remember where such a wellness experience takes place and revisit the place to remember such a pleasurable experience. However, things could become very problematic if the experiment involved addiction. Conditional Place Preference (CPP) is an experimental paradigm for studying the mechanism of addictive behaviors badociated with a pleasant experience. It has long been believed until recently that the release of dopamine hormone in the mesolimbic pathway of the brain was the key to CPP. However, since dopamine-deficient mice were found to have CPP, the brain CPP pathways remained inaccessible. Meanwhile, the hippocampus, the region of the brain responsible for spatial memory, has not been considered to be involved in the CPP.

Under the direction of C. Justin Lee, researchers at the Center for Cognition and Sociality at the Institute of Basic Sciences in Daejeon, South Korea, have identified a new mechanistic element of CPP, mu-opioid receptors (MOR) expressed in astrocytes. of the hippocampus. Opioids include endorphins (the transmitters of our brain's wellbeing) or morphine (a major painkiller) that can make people feel relaxed or happy and addictive. Much has been studied about neuronal MOR, but has failed to fully understand the mechanism of CPP. The research team looked at seemingly unlikely cells that were thought to provide only support and protection for neurons, astrocytes (that is, a cell type of cells other than neurons) in the brain . They have reduced their target range to the astrocytic MOR of the hippocampus because that is where the spatial memory is formed.

In their experiments on mice, the researchers placed the mice in two separate spaces with a door in the middle. One compartment was black with a stainless steel floor and another was black and white striped. At first, they let the mice move in both spaces through the door to find their preferred and not preferred location. Then, they administered DAMGO mice or morphine in their non-preferred spaces to condition only the opioids controlling the mouse CPP. After this conditioning, the researchers again let the mice freely explore the two separate spaces and observed which room the mice preferred. Experiments have shown that exogenous opiod injection (DAMGO) or morphine activates astrocytic MORs in the hippocampus to release glutamates. These excitatory neurotransmitters increase synaptic transmissions at the Schaffer collateral-CA1 synapse in the hippocampus, responsible for spatial memory acquisition to induce CPP. The increase in synaptic activities technically calls for long-term potentiation (PLT).

To determine whether astrocyte MORs are the essential component for initiating opioid-induced CPP, the researchers proceeded to genetically inactivate specific astrocyte MORs in the hippocampus and see if CPP is induced by DAMGO treatment. The researchers found that DAMGO treatment did not induce CPP without astrocytic MORs from the hippocampus. These results indicate that the astrocytic MORs of the hippocampus are essential for the induction of CPP, in addition to mesolimbic neuronal MORs.

Dr. Min-Ho Nam, first study Author:

There has long been a dogma on conditioned place preference (CPP): interneuronal MOR in the mesolimbic dopaminergic system is the only key to CPP. To overcome this dogma, we adopt multidisciplinary strategies including genetics, histology, electrophysiology and behavioral tests. "

This study notably made it possible to verify that the astrocytic MOR of the hippocampus were the place where the artificial opioids (morphine) and biological (endorphin replaced by DAMGO) began to induce the acquisition of a contextual memory badociated with pleasure. "Astrocyte is the most abundant cell type in the brain.This astrocyte-oriented study helps to better understand how humans prefer a certain place where a happy memory is badociated.We hope this study will fuel the pbadage from neuro-centric to – centric in the field of brain science, "says the corresponding author of this study, Dr. Lee.