Rozkład białka c-Fos w całym mózgu podczas uczenia apetytywnego : praca doktorska

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Rozkład białka c-Fos w całym mózgu podczas uczenia apetytywnego : praca doktorska

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Title: Rozkład białka c-Fos w całym mózgu podczas uczenia apetytywnego : praca doktorska

Abstract:

Learning is the ability of organisms to change their behavior as a result of past experience. Learning enables adaptation to constantly changing environment, and thus proper response to positive (appetitive) and negative (aversive) stimuli. An appetitive stimulus triggers motivational responses aimed at approaching a reward, an aversive on the other hand induces withdrawal (avoidance and/or escape). Learning occurs through synaptic plasticity which is the brain's ability to alter the strength of connections between neurons. On cellular level synaptic plasticity is related to neuronal activity that drives functional and structural changes within synapses. As a consequence a subject can retain past experiences in its memory and adapt its behavior to similar situations in the future. Thus, synaptic plasticity is crucial for the development of appetitive and aversive behavior and organism survival. On the other hand, these mechanisms are also involved in the development of mental illnesses. Therefore, understanding the neuronal mechanisms involved in synaptic plasticity is crucial. In comparison to the neuronal changes underlying aversive behavior those associated with appetitive learning have been poorly characterized. Therefore, the aim of the present study was to map neuronal activity in the brain occurring during appetitive learning. For this purpose, we used a mouse model in which appetitive learning was based on place preference for a 10% sucrose. The c-Fos protein was used as a marker of neuronal activation that is related to plasticity, and its expression was imaged by light-sheet fluorescent microscopy (LSFM). This approach allowed creating a global map showing the increased c-Fos expression in nearly 170 brain structures. Next, in silico analysis of neuronal projections between the most activated brain regions were conducted. It was shown that there is a large number of connections between the central nucleus of the amygdala (CeA) and several other structures that were activated during the training. Next, the types of neurons in which c-Fos expression occurred in response to appetitive learning were identified. Since CeA mostly consists of inhibitory neurons, experiments were conducted on 3 populations of neurons: VIP+, PV+ and SST+. It was shown that during learning of appetitive events, c-Fos is expressed mainly in SST+ neurons and to a small extent in VIP+ and PV+. The last part of the study involved electrophysiological characterization of SST+ neurons in CeA. It was shown that depending on the CeA part, SST+ neurons are divided into two groups that generate a different type of discharge. Furthermore, it was shown that learning positive events results in the increased excitability of SST+ neurons in the CeA. The present study shows that appetitive learning leads to global activation of many brain structures. Moreover, it was found that CeA is crucial for the appetitive learning by the activation of SST+ neurons.