Przetwarzanie informacji o nagrodach naturalnych i farmakologicznych w mózgu myszy : praca doktorska

Bijoch, Łukasz

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Przetwarzanie informacji o nagrodach naturalnych i farmakologicznych w mózgu myszy : praca doktorska

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Title: Przetwarzanie informacji o nagrodach naturalnych i farmakologicznych w mózgu myszy : praca doktorska

Abstract:

Appropriate response to appetitive stimuli in the environment is a crucial skill for animals, enabling their survival and reproduction. While some psychoactive substances also induce pleasurable sensations, their actions rely on the pharmacological influence on neurons. Hence, two types of appetitive stimuli are distinguished: natural and pharmacological rewards. Pharmacological rewards are associated with addiction, and at the core of substance dependence are changes in the quantity and quality of neuronal connections induced by psychoactive substances, known as plastic changes. Plastic changes also occur physiologically in the brain and are considered as the molecular bases of memorizing. It is suspected that the plastic changes induced by pharmacological rewards occur in brain regions that usually process natural rewards, encoding pathologically persistent memories of the drug. Using two mouse models of reward exposure, I investigated whether information about them is indeed processed by the same brain regions. As natural reward, mice had access to a sweet sucrose solution for two hours daily. As pharmacological reward, mice received intraperitoneal injections of a cocaine saline solution. Animals were exposed to these rewards either once or for seven consecutive days. To investigate brain structures engaged by these rewards, I examined the level of c-Fos (a protein associated with neuronal activity and synaptic plasticity) throughout the entire brain. Utilizing optical tissue clearing and light sheet microscopy, I found that both rewards engaged structures in extensive brain regions. The pattern of increased activity partially overlapped for both rewards, but in the case of many areas it was specific only to exposure to cocaine or sugar. By analyzing the increase of c-Fos level after single vs. multiple exposures of animals to sweet water, I observed that it was higher after a single administration. In the case of cocaine, these effects were opposite, and after seven days of drug administration, over half of brain structures showed altered activity. I also examined the processing of information about sugar and cocaine at the level of individual neurons within the central nucleus of the amygdala (CeA). CeA processes emotionally significant stimuli and consists of two parts: medial (CeM) and lateral (CeL). Using electrophysiological techniques, I investigated plastic changes induced by rewards in CeA. I found that both sugar and cocaine induce plastic changes in CeM. Electrophysiological analysis showed that these plastic changes resulted in enhanced synaptic strength reaching CeM. On the other hand, plastic changes in CeL were observed only in animals exposed to cocaine, and they resulted in a weakening of synaptic strength. I confirmed the involvement of CeA in processing both rewards by studying the behavior of animals with altered CeM activity. With chemogenetic tools, I blocked the motivation of animals to sweet water and delayed the onset of some behavioral effects induced by cocaine. I also discovered in CeA a population of dopamine sensitive neurons with two types of receptors: DRD1 and DRD2. I found that neurons in CeL express only DRD2, while in CeM, they have either DRD1 or DRD2 on their surface. I found that cocaine and sugar differently modulate the activity of these neurons in CeM. Cocaine increases the spontaneous activity of neurons with DRD1 and decreases those with DRD2. Sugar, on the other hand, increases the spontaneous activity of neurons with DRD2 and decreases those with DRD1. In summary, the results of the study indicate that information about sugar and cocaine is processed differently in the brain. The distinct nature of these rewards requires the characterization of individual reward system models. Information about sugar and cocaine is also variably processed by CeA neurons, but a precise understanding of these mechanisms requires consideration of the roles of different neuron populations.