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Browsing by Subject "varhaiselämän stressi"

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  • Jalonen, Sonja (2023)
    Early life stress (ELS) has been associated with the development of psychiatric disorders such as anxiety and depression later in life. The central hypothesis is that these disorders are caused by a malfunctioning of the serotonin system and serotonin (5-HT) produced in the dorsal raphe nucleus (DRN). The DRN is anatomically connected to the medial prefrontal cortex (mPFC), especially to the infra- and prelimbic cortex, where 5-HT modulates behaviors such as impulsivity and cognitive flexibility. The DRN and mPFC mediate with low-frequency network oscillations, which are indicative of the state of the network and its funtional connectivity, as disturbances in these network oscillations have been connected to neuropsychiatric disorders. The aim of the thesis is to investigate whether and how ELS can influence the local field potential (LFP) activity of the mPFC and DRN and the functional connectivity of the DRN and mPFC. This is researched by characterizing and comparing the LFP activity recorded in the DRN, where 5-HTergic neurons are located, and in layer 5 of the infralimbic area of the mPFC. To accomplish these aims, a well-established animal model of early-life stress, the limited bedding and nesting model (LBN), was used. The model causes fragmented maternal care due to the stress of the dam, which in turn leads to the stress of the pups. Simultaneous multi-site recordings of LFP and multi-unit activity (MUA) within DRN and mPFC were performed in vivo during postnatal days (PND) 10-11 from control and LBN pups to characterize the network activity of these two brain areas and then investigate possible changes in their functional connectivity. The efficacy of the LBN model was determined by the observed decreased weight gain of LBN animals compared to controls. From the data, the LFP activity of the DRN and mPFC were characterized. The activity was characterized as power spectrum, wavelet spectrum, and MUA with DRN showing discontinuous activity with low signal-to-noise ratio and low frequency theta oscillations (4-12 Hz), while mPFC showed almost continuous activity with higher signal-to-noise ratio and developing gamma oscillations (20-50 Hz). The power of LFP signal of the areas was not found to be affected by ELS. To investigate if the coupling by synchrony between DRN and mPFC networks is altered by ELS, I analyzed wavelet coherence by computing coherence values between LFP signals in DRN and mPFC in a control and ELS for frequencies from 1 to 50Hz. The functional connectivity was affected by ELS. Statistically significant changes were observed in wavelet coherence in the lower frequencies of 1-2.8 Hz between the control and LBN treatment, suggesting impaired synchronization between DRN and mPFC at 1-2.8Hz frequency range immediately after ELS exposure at PND 10-11 mice. Caveats of the study were low signal-to-noise ratio of the recordings, the small group size of LBN animals (n=5) as well as the uneven sex distribution (male n=11, female n=3) which prevented the sex-based comparison of the effects of ELS. The thesis examines postnatal LFP brain activity in the DRN and mPFC and the functional connectivity between these brain areas. The results of the thesis show that ELS exposure is able to influence the functional connectivity of these two brain regions. The results support previous findings, which have found alterations in the functional connectivity of the neural networks underlying neuropsychiatric disorders in adulthood. The findings of this thesis suggest that ELS could affect the functional connectivity of a developing network and thus increase the risk of the development of neuropsychiatric disorders. Further studies are needed with larger group size, even gender balance, and better signal-to-noise ratio of recordings.