Projects
Our main goal is to understand the basis of memory formation. In particular, we are focused on explaining the molecular and cellular bases of appetitive memory - remembering positive events. Substance abuse is a particular case of appetitive memory - one that is virtually irreversible. We aim to find out the mechanisms of addiction development.
Cellular bases of reward learning and addiction development
By changing the number and strength of synapses, the brain integrates and stores information about the surrounding world. This process is called synaptic plasticity and is the basis of memory formation. We focus on a specific type of synaptic plasticity that has been linked to brain development and drug addiction - the formation of silent synapses. These immature excitatory contacts do not participate in basal synaptic transmission, hence the term "silent". However, they are activated when increased neuronal firing leads to synapse strengthening. Thus, the appearance of silent synapses signifies an increased capacity to learn, such as in young, developing brains. Unfortunately, certain drugs of abuse have the capacity to induce silent synapses in the adult brain, which ultimately leads to the formation of strong, drug-related memories. In our lab, with behavioral, electrophysiological, and optogenetic tools we study the formation and fate of silent synapses in regard to natural and addictive rewards.
Neurocircuitry of the Central Amygdala
The central amygdala is a brain structure processing stimuli with a strong emotional context. Thus, it is instrumental in assigning valence to incoming stimuli - positive or negative. In this project, we are studying how the central amygdala deals with stimuli with non-obvious valence - drugs of abuse.
Drugs like cocaine, exhibit pleasing effects and are categorized as rewards, but no doubt they also have a bold aversive component. With electrophysiology, in vivo two-photon microscopy, and chemogenetic techniques (DREADDs) we found a vast and long-lasting reorganization of the Central Amygdala circuitry upon cocaine exposure.
Volumetric tracking of the brain activation upon drug exposure
Natural rewards, such as food are appetitive (positive) stimuli available in the natural environment. Drugs of abuse are also rewarding, but their actions rely strictly on their pharmacological properties. Thus, the still remaining question is whether they are being processed by the same brain areas. Thus, we are studying whether drugs and natural rewards activate similar brain circuitry.
With tissue-clearing techniques, immunohistochemical labeling of activity-related genes, and volumetric imaging with a light-sheet microscope we are tracking which brain parts are involved in reward processing. This universal mapping allowed us to create a general pattern of brain activation after exposure to natural and addictive substances.