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Browsing by study line "Neurotiede"

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  • Lewis, Serena (2021)
    Histamine receptors are known to be expressed throughout the peripheral nervous system and are involved in regulating the gut and immune system. The gut-brain axis, which consists of bidirectional signaling between the central nervous system and gastrointestinal tract, links gut functions to emotional and cognitive controls in the brain. Many animal models are known to express histamine receptors in their gut and brain tissue which can be altered by a compromised gut-brain axis like stress. Histamine receptors also play an important role in many gastric and intestinal disorders. However, the precise expression pattern of histamine receptors in zebrafish gut tissue is unknown, as is whether their expression levels also change with stress. Here, I show that zebrafish gut contains several histamine receptors, but their role involving stress within the gut remains unknown. I found that histamine receptors hrh1 and hrh3 as well as the enzyme that synthesizes histamine, histidine decarboxylase (hdc), are expressed in zebrafish gut and brain in wildtype and hdc knockout adult zebrafish using in situ hybridization. Stress induction on wildtype male zebrafish through chronic social defeat and analysis of histamine receptor and hdc mRNA levels using quantitative real time PCR showed no differences in subordinate, dominate, or control fish. However, it did provide quantitative data that hrh1, hrh2, and hdc mRNA expresses in the adult gut. My results demonstrate the first data to suggest histamine receptors are expressed in zebrafish gut, and that even though stress can alter the gut-brain axis, it may not do so through the regulation of these receptors.
  • Knapič, Samanta (2023)
    White matter (WM) structural connectivity alterations have been linked to depression. This study aimed to identify structural connectivity metrics associated with Major depressive disorder (MDD) and predictive of different symptom phenotypes. The study sample included N=29 control and N=86 subjects with MDD who underwent a clinical interview, Mini-International Neuropsychiatric Interview (MINI), and assessment of depression symptoms severity. Using a 3T MRI scanner, diffusion tensor imaging (DTI) was employed to capture WM connectivity markers at baseline. While no distinct differences between control and MDD groups were observed at the whole-brain network level, significant alterations were evident at the node level. Clinical group demonstrated enhanced connectivity, particularly in the DefaultB and LimbicB subsystems, as evidenced by measures such as eigenvector centrality. Furthermore, notable differences were observed in clustering coefficient and local efficiency, predominantly in DefaultB, LimbicB, and VisPeri networks, with MDD patients showing higher connectivity. Analysis of the association between WM structural connectivity measures, both global (e.g. global efficiency) and local (e.g. clustering coefficient) with MDD symptom scores and related symptoms, revealed no significant correlation at the whole-brain level, both at baseline and post-intervention. Distinct patterns were identified when evaluating node-level metrics averaged across networks, which together with group differences, point to MDD patients exhibiting characteristics consistent with regular networks. Hierarchical clustering based on standardized baseline DTI structural connectivity within the clinical cohort revealed three distinct clusters of MDD patients, with the first cluster exhibiting a higher WHO-5 score, indicating a potential association with better well-being. These findings provide insight into MDD-specific brain regions’ structural alterations and underscore the heterogeneity of depression symptom profiles. Further research is needed, including a higher sample size and control for confounding factors.
  • de Sena, Sofie (2022)
    The analysis of gaze behaviour is nowadays commonly employed to help with the diagnosis and exclusion of differential neurological conditions as well as to help researchers better understand cognition in the early stages of life. However, its application in the developmental evaluation and follow-up of children with early-onset epilepsy has not been profoundly studied yet. Therefore, the current study aimed to investigate the association between the gaze behaviour of infants with early-onset epilepsy and their future neurodevelopmental outcome. To study the association and its predictive ability, three models were created. Sixty-three infants with epileptic seizure onset before 12 months of age participated in the study with the voluntary consent of their parents. Infants’ gaze behaviour was recorded with Tobii Pro-X3-120 at two measure points. The results showed infants’ initial ability to fixate their gaze, changes in their gaze shift probability in the first 12 months of life, and structural aetiology to be significantly associated with the infants' developmental outcome at 24 months of age. Where the structural aetiology was significantly associated with poorer developmental outcome, good initial fixation ability and improvements in the infants’ gaze shift probability during their first year of life were significantly associated with more positive outcome. These findings suggest that gaze behaviour at an early age is an essential predictor of later development in infants with early-onset epilepsy. Hence, eye-tracking could provide means to evaluate the later neurocognitive outcome of infants with early-onset epilepsy at an early age.
  • Grönlund, Katja (2023)
    Nuclear receptor subfamily 5 group A member 1 (NR5A1) is a master regulator of both steroidogenesis and gonadal development. Disruptions of NR5A1 can result in differences in sexual development (DSD). With proven interspecies differences in NR5A1 functioning and human material not being available, human stem cells are one of the most achievable, ethical, and accurate models to study the earliest developmental stages of foetal life. However, in currently existing human stem cell-derived gonadal models the expression of NR5A1 has been insufficient without artificial induction due to the lack of knowledge of its distinct biological mechanisms, endogenous ligands, and co-factors. A functional reporter cell line would enable high throughput microscope screening of differentiation protocols with expressed NR5A1. The aim of this thesis was to generate a functional monoclonal human embryonic stem cell (hESC) reporter line for the gene NR5A1 with Alt-R CRISPR-Cas9 ribonucleoprotein (RNP) complex. Firstly, an efficient guide RNA was determined for NR5A1 by T7 assay, and a homology-directed repair (HDR) donor plasmid was designed based on it. Secondly, monoclonal hESC lines were generated with the Alt-R CRISPR-Cas9 RNP complex knock-in method and HDR donor plasmid via electroporation and single-cell sorting. Finally, monoclonal hESC reporter lines were screened with Touchdown PCR and a functionality analysis based on fluorescence and mRNA expression was performed. Two monoclonal hESC reporter lines H9-NR5A1-eGFP cl. 1 and dual-inducible H9-NR5A1-DDdCas9VP192-eGFP cl. 28 were established by using Alt-R CRISPR-Cas9 RNP complex. However, a functional validation performed on H9-NR5A1-DDdCas9VP192-eGFP cl. 28 cells showed the cell line to be non-functional upon NR5A1 upregulation regardless of the expressed eGFP mRNA detected with RT-qPCR.
  • Haikonen, Joni (2019)
    Kainate receptors are known to regulate neuronal function in the brain (Li, H., & Rogawski, M. A. (1998), Braga, M. F. et al. (2004), Lerma & Marques (2013), Carta, M (2014)). In the amygdala, they have been shown to affect synaptic transmission and plasticity, as well as glutamate and γ-aminobutyric acid (GABA) release (Li, H. et al. (2001). Braga, M. F. et al. (2003), Braga, M. F. et al. (2009), Aroniadou-Anderjaska, V. et al. (2012), Negrete‐Díaz, J. V. et al. (2012)), however, their role during development of the amygdala circuitry is not known. In the present study, we wished to understand how GluK1 kainate receptors regulate synaptic population activity and plasticity in the developing amygdala by using extracellular field recordings in P15-18 Wistar Han rat pup brain slices. Since field excitatory postsynaptic potentials (fEPSPs) are not commonly measured from the amygdala, we first sought to pharmacologically characterize the basic properties of the extracellular signal, recorded from the basolateral amygdala in response to stimulation of the external capsulae (EC). Having confirmed the validity of the fEPSP as a measure of postsynaptic population response, we were able to show that blocking GluK1 with (S)-1-(2-Amino-2-carboxyethyl)-3-(2-carboxy-5-phenylthiophene-3-yl-methyl)-5-methylpyrimidine-2,4-dione (ACET), a selective GluK1 antagonist, had no effect on the fEPSP. Furthermore, activation of GluK1 with RS-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a GluK1 agonist, reduced the amplitude of the fEPSP, without affecting its slope, suggesting an increase in inhibitory signaling within the network. Blocking GABAergic activity with GABAA- receptor antagonist picrotoxin significantly reduced the effects of ATPA. Additionally, the increase in inhibitory signaling due to the activation of GluK1 was confirmed with whole-cell voltage clamp, by measuring spontaneous inhibitory postsynaptic current (sIPSC) frequency. Activation of GluK1 heavily increased sIPSC frequency in the basolateral amygdala neurons. Finally, we were also able to show that activation of GluK1 with ATPA strongly attenuates LTP induction. These results show that GluK1 kainate receptors play a vital role in the modulation of synaptic transmission and plasticity in the developing amygdala.
  • Junell, Niklas (2021)
    Hippocampal place fields play a key role in spatial navigation. New place fields are formed during exploratory behavior through long-term potentiation (LTP) and long-term depression (LTD) of synaptic inputs to place cells located in hippocampal CA1. Recently, a novel form synaptic plasticity termed behavioral time scale plasticity (BTSP) has been demonstrated to occur in CA3–CA1 synapses in vitro. BTSP can potentiate synapses that were active several hundred milliseconds before or after a priming event such as a strong and prolonged somatic depolarization. This plasticity rule could be an important complement to well-established spike timing dependent plasticity (STDP) which associates neuronal inputs with outputs at a time scale less than a few tens of milliseconds. The aim of this thesis was to determine whether high frequency antidromic stimulation can act as a priming event that enables BTSP induction in CA1 pyramidal neurons. The underlying assumption was that antidromic stimulation could prime BTSP via action potential backpropagation. High frequency bursting of CA1 neurons in hippocampal slices was achieved with 100 Hz antidromic stimulation of CA1 axons in the alveus. Schaffer collaterals were stimulated 500 ms before or after CA1 burst firing with intensities that were subthreshold for LTP when unpaired. I found that high frequency firing did not enable LTP induction during either of the two experimental protocols, suggesting that neuronal output alone is insufficient for priming BTSP.
  • Failla, Laura (2019)
    The vagus nerve is the longest nerve of the autonomic nervous system. It innervates, among other organs, the stomach, the lungs and the heart, and it reaches several areas of the brain, including the locus coeruleus and the amygdala. The invasive stimulation of this nerve (vagus nerve stimulation, or VNS) is a currently used method for the treatment of refractory epilepsy and pharmaco-resistant depression (Englot et al. 2011; O’Reardon et al., 2006), but the impact that this technique might have on the brain physiology and functions is still under investigation. Various studies (Frangos et al., 2015; Yakunina et al., 2016; Hansen, 2019) have shown that VNS increases noradrenaline production in the brain, a neurotransmitter that is involved in several cognitive processes, such as sleep and mood control. Furthermore, in a study on patients with epilepsy, by Sun et al. in 2017, VNS appeared to have a clear effect on working memory and emotion-attention interaction. Nevertheless, VNS presents all the risks and potential complications that characterize invasive procedures requiring surgery. Therefore, research is now focusing on safer, non-invasive alternatives, such as transcutaneous vagus nerve stimulation (tVNS). This technique allows to stimulate the nerve through its sensory fibres, located in the cymba and tragus of the ear. The scope of the present study was to see whether tVNS would have the same effects on cognitive and affective functions as VNS. The sample for this single blind placebo-controlled study was composed of 30 healthy subjects between 18 and 45 years old. Exclusion criteria included a history of psychiatric, neurological or cardiovascular diseases. All subjects were asked to complete a computer-based task, the Executive Reaction Times-Test. Throughout the test the subjects alternately received an active or a placebo stimulation, and their brain activity was recorded for the whole duration of the test using a 64-channel EEG cap. The Executive-Reaction Times-Test was chosen for this study because it allows to test multiple executive functions simultaneously. The subjects were presented with a series of stimuli on a screen and were asked to react as fast and accurately as possible to “Go” signals, and to refrain from responding when “NoGo” signals appeared. The test started with a triangle pointing either up- or downwards, followed by a brief pause and a traffic light image. The traffic light showed either a red or a green light and included an emotional distractor in the form of a spider or a flower. The red and green lights were alternately used as “Go” or “NoGo” signals, and the rule changed at each test block. In order to complete the task, subjects needed to keep the image of the triangle in their working memory, stay focused on the stimuli and be ready to react or be able to inhibit any responses, thus several main executive functions are being tested: inhibitory control, working memory, attention and emotion-attention interaction. Active stimulation was delivered through clip electrodes that were attached to the tragus of the left ear, whereas placebo stimulation was delivered through clip electrodes that were attached to the left ear lobe. The subjects were not aware of the difference between the two locations. Only the data of 18 subjects was used for the results analysis, because of technical difficulties with the EEG data (some recordings were too noisy, some presented flat channels). The behavioural data was divided into reaction times and errors, which were separately analysed. The EEG data was used to extract the amplitudes of the ERP peaks N2 and P3. The former is a negative peak visible at 200-350ms; the latter is a positive peak visible at 300-500ms. Previous studies have shown the peaks to be associated with response conflict and inhibition (Falkenstein et al., 1999; Donkers et al., 2004; Smith et al., 2013). The behavioural data analysis did not show any significant effect of stimulation on reaction times or error amounts. The ERP analysis, instead, returned interesting results. We observed a main effect of stimulation (p=0.04) in “NoGo” conditions. There was a significant reduction in the N2P3 amplitude and the N2 amplitude in “NoGo” conditions, with active stimulation compared to placebo. These results seem to suggest that with tVNS, fewer cognitive resources are allocated to resolve the inhibitory task, without worsening the subjects’ performance. The lack of significance in the behavioural results might have been due to a ceiling effect, with the Executive Reaction Times-test being too easy for our sample. Overall, the number of errors was too low to conduct a reliable statistical analysis. Nevertheless, the effects we observed on brain physiology would suggest that further research is needed to explore the actual impact of tVNS on cognitive and affective functions.
  • Kontio, Salla (2022)
    Spontaneous and voluntary movements of infants effectively reflect the developmental integrity of brain networks. When it comes to the research of motor development, the use of intelligent technology has shown to provide objective, automated, and scalable methods for movement assessment. In addition to intelligent technology, research on the usage of surveys – in this case parental surveys – has looked at the untapped potential that parental viewpoint. Guardians have a unique and holistic image of the child’s development, thus data from parental surveys could be used to further help us to assess infant’s development. For this study, I studied how the parents’ time estimate on the positions their child spends time in holds up against the machine-learning based data obtained with the smart jumpsuit. Using the data acquired from the smart jumpsuit during the recordings, we can see the amount of time the child spends in each position. Aim was to study the relationship between these variables and gain further understanding on the utilization of parental perspective in the assessment of motor development. Data was collected from 19 video recordings and videos were annotated with Anvil video annotation software for child’s posture and movements, and the annotations were used for training a machine learning-based classifier of the smart jumpsuit. Only data regarding postures was extracted for further analysis. Parental surveys were carried alongside of recordings. In the survey of parental estimate, we asked the parent to assess how much time the child spends in a specific posture. Positions which the survey focused on were prone, supine, side, sitting, crawling, and standing. Data from the recordings as well as data from parental surveys were visualized with radar plots. In addition, correlation was visualized in a linear regression. Positions which had both correlation of higher than 0.5 and a significant p-value were sitting (p < .001**), crawl posture (p < .05*), standing (p < .001**), and supine (p < .05*). Results suggested that parents were successfully assess the time spent in following postures: sitting, crawling, standing, and supine. This indicates that parents have a holistic understanding of their child’s motor development, and the knowledge could be useful in the overall assessment of development, especially when it comes to children with developmental delay. The parent’s ability to accurately assess a child’s motor development helps the parent support the child’s development.
  • Kõbin, Mihkel (2020)
    Intersectins (ITSNs) are important scaffold and adaptor proteins that play an important role in various cellular processes such as endocytosis. Although we know a lot about their function, there is little information on the regulation of these proteins. On the other hand, microRNAs have been shown to have an extensive function in regulating numerous genes in animals and their dysfunction is credited for down regulation of many proteins. In this study, I demonstrate that microRNAs are potential regulators of ITSNs in HEK293 cells and human neuronal cell cultures. In this study, I cloned 3’UTRs of different isoforms of intersectins (ITSNs) and microRNAs to the expression vectors to express them in cells. I then transfected HEK293T or neuronal stem cell line (HEL47.2) with the constructed vectors and used various methods to analyse the effect of microRNAs on the expression of ITSNs. The main methods I used were dual-luciferase assay, reverse transcription quantitative PCR and western blotting, human neuronal stem cell culturing and lentiviral transduction. My results demonstrate that there were two microRNAs that stood out from other and had a significant downregulation of ITSNs mRNA levels in HEK293T cells. Those were miR-124 and miR-19. However, in the human neuronal cell line I did not observe a significant alteration of the ITSNs transcript level. Additionally, I suggest that the given microRNAs regulate protein levels by promoting the decay of the ITSN transcripts. However, more studies are needed to show a stronger causative effect of microRNAs on ITSNs. Subsequent studies should also look at how multiple microRNAs can influence gene expression cooperatively.
  • Ruuska, Janika (2022)
    Individuals suffering from anorexia nervosa (AN) have one of the highest mortality rates of all psychiatric disorders, as a consequence of health complications that follows severe malnutrition. The impairments in cognitive flexibility, including an extreme focus on restricting food despite a rapid decline in body weight in AN, also plays an important role in the development of the disorder and has been suggested as a hallmark of AN. This cognitive inflexibility, common among many psychiatric disorders such as depression and obsessive-compulsive disorder, is linked to alterations in serotonin (5-HT) signaling in the medial prefrontal cortex (mPFC). Reduced 5-HT2A receptor activity and potentially increased 5-HT1A receptor activity are evident in the mPFC in individuals with AN and may be linked to impaired cognitive flexibility, however, the mechanisms through which 5-HT and inflexibility interact in AN are not fully understood. A better understanding of this link could pave the way toward more effective pharmacological treatments for AN. Psilocybin, a psychedelic compound produced by so-called “magic” mushrooms, has a high affinity for several 5-HT receptor subtypes including 5-HT1A and 5-HT2A receptors, and has now been empirically demonstrated to increase cognitive flexibility in individuals with major depressive disorder (MDD). In this study, we sought to understand how the development of pathological weight loss and/or psilocybin administration influenced the expression of RNA molecules of 5-HT2A and 5-HT1A receptors expression in the mPFC of rats. To this end, we used the activity-based anorexia (ABA) model, the only experimental model known to elicit voluntary reductions in food intake and voluntary hyperactivity that leads to rapid body weight loss in the majority of animals exposed to ABA conditions. Outcomes were compared against an age-matched control group that were not exposed to the ABA paradigm. Animals were administered psilocybin (1.5 mg/kg) or saline (control) and 4-10 days later brain tissue was collected for processing. Receptor expression was detected using a novel multiplex RNA fluorescent in situ hybridization (FISH) technology, RNAscope®. The main aim of this study was to examine changes in the expression of RNA molecules of 5-HT2A and 5-HT1A receptors in the mPFC elicited by ABA conditions and determine whether these were ameliorated by the administration of psilocybin. We found that animals exposed to ABA demonstrated a significant reduction of 5-HT2A receptors’ RNA levels in the mPFC, and that this was not influenced by psilocybin treatment. There have been reports from clinical trials that individuals with AN experience “less than expected” subjective effects from psilocybin, which may be explained by reduced expression of RNA molecules of 5-HT2A receptors in the mPFC, and is supported by our results in rats. Taken together, these results highlight a specific serotonergic mechanism that could underly the development of pathological weight loss and offers insight into possible issues with the therapeutic application of psilocybin for AN. Future studies will need to examine the effects of psilocybin during a more acute period following treatment to define these effects. Moreover, whether or not the reduced 5- HT2A receptors’ RNA level expression induced by ABA is restored with body weight recovery should be determined.
  • Nurmi, Joonas (2022)
    Goal-directed behavior is reliant on the ability to choose correct actions to perform given the context of the situation while minimizing the interfering effect of goal-irrelevant stimuli. The ability to suppress inappropriate responses is called response inhibition. It can be seen as a higher order cognitive function which is one of the cornerstones for adaptive behavior in ever changing environment. Neural oscillations have been previously used to study at the neuronal processes underlying cognitive processes such as response inhibition. Neural oscillations are rhythmic fluctuation in the excitability of a neuron or a group of neurons. These temporal windows of excitability are thought to underlie efficient communication by changing the efficacy of the synaptic transmissions between neurons/group of neurons. Although, a lot has been uncovered about the different oscillations and their possible role in response inhibition, very little is known how the spectral content (power of a frequency) adapts across as the animal is learning to suppress their responses to new novel stimuli. This kind of learning associated spectral content adaptations has been observed previously in humans during motor learning for example. In the current study we aimed to look how spectral content adapts as the animals learn to suppress their responses to novel stimuli. We used head fixed rats on a treadmill that were trained to perform Go/NoGo task. Each rat performed 1-4 learning scenarios during which the “rules” for Go/NoGo task changes in an attentional set-shifting paradigm. We measured EEG from most of the rat’s cortex. EEG was measured from the point where the rat was first introduced to these novel stimuli until the rat had learned the new stimulus-response contingences. This EEG was divided into learning stages and the power spectrum was calculated for each of them. We observed power peaks centered around 1Hz, 2Hz, 4Hz, 8Hz and 11Hz across learning stages. However further analyses comparing average power across learning stages showed that these changes were not statistically significant. Thus, we did not observe gradual changes in power while rats were learning to suppress their responses to novel stimuli.
  • Nykänen, Heidi (2022)
    Parkinsonin tauti on maailman yleisin hermorappeumaa aiheuttava liikehäiriösairaus. Taudin ilmaantuvuus- ja esiintyvyysluvut ovat jatkuvassa nousussa, mitä väestön ikääntyminen ei yksin selitä. Taudin patologisia löydöksiä ovat alfasynukleiinin kertyminen ja vääränlaisesta laskostumisesta johtuva aggregaatio, Lewy neuriittien ja kappaleiden kertyminen sekä dopaminergisten hermosolujen solukato mustatumakkeesta. Taudin pidemmälle edenneille vaiheille on tyypillistä vaikea toimintakyvyttömyys ja elinajanodotteen lasku. Nykyiset hoitomuodot niin Parkinsonin taudille, kuin muillekin hermorappeumasairauksille ovat ainoastaan oireita lievittäviä. Onnistuneeseen lääkekehitykseen vaaditaan parannusta eläinmallien validiteetin jokaisella alatasolla. Parkinsonin taudin käytössä olevissa prekliinisissä eläinmalleissa on huono ilmivaliditeetti monien potilailla tehtyjen patologisten löydösten puuttuessa. Tässä tutkielmassa esitän uudenlaisen SynFib rottamallin Parkinsonin tautiin. Eksogeenisesti valmistettuja ihmisen alfasynukleiinifibrillejä injisoitiin yhdessä alfasynukleiinia ekspressoivien virusvektoreiden kanssa mustatumakkeeseen. Injektio aiheutti intensiivisen ja etenevän alfasynukleiinista johtuvan patologian ja merkittävän dopaminergisen soluvaurion. Taudin etenemistä seurattiin pitkittäistutkimuksessa positroniemissiotomografialla ja toiminnallisia puutteita arvioitiin synapsitiheydessä, inflammaatiossa ja dopaminergisessa järjestelmässä 16 viikon ajan. Havaitsin aivokudoksen tulehduksen ja dopaminergisen ipsilateraalisen soluvaurion lisääntyneen merkittävästi. Kahden viikon kohdalla synapsitiheys oli merkittävästi vähentynyt ipsilateraalisesti ja taudin leviäminen kontralateraaliselle puolelle oli alkanut.
  • Haapala, Anu Johanna (2023)
    Introduction: Oxidative stress occurs in cells when reactive oxygen species are generated as a by-product of oxygen metabolism and start to accumulate excessively. While extensive oxidative stress is highly detrimental to the cells, trophic factors help them survive. Trophic factor MANF has interested especially Parkinson’s disease researchers, but recent findings suggest that MANF plays a role in many diseases, also ones with an early childhood-onset. For this reason, it is important to investigate MANF function in different cell types. We have studied how MANF-knockout human embryonic stem cells react to oxidative stress compared to wild-type human embryonic stem cells, by exposing the cells to hydrogen peroxide and ethanol. Results: MANF-knockout human embryonic stem cells were more sensitive to oxidative stress than wild-type cells, but the variation between measurements was remarkable and the differences were statistically insignificant. We found that a transcription factor of our interest localized in the cell nuclei of MANF-knockout cells upon oxidative stress exposure. Such a nuclear translocation did not occur in wild-type cells. Moreover, we found that high concentrations (>2%) of ethanol reduced the viability of cells in only four hours. Discussion: Our findings suggest that MANF-knockout human embryonic stem cells react to oxidative stress differently than wild-type cells. Additional studies are necessary to clarify whether MANF-knockout human embryonic stem cells are indeed more sensitive to oxidative stress than wild-type cells. In the future, it would be interesting to inspect whether MANF protects human embryonic stem cells when the cells are exposed to physiologically relevant ethanol concentrations for longer periods of time.
  • Jakkli, Meera (2020)
    Neural Oscillations at large-scale local and global neural synchrony levels can be detected at the scalp using electroencephalography. This neural activity presents itself in a varied range of frequencies referred to as ‘Brain Waves’. These frequency bands have cognitive significance and have been implicated in several neural functions due to its important role in communicating with functionally-similar but spatially-distinct brain regions. Frontal Asymmetry is the difference in activity between the right and left hemispheres in frontal areas of the brain recorded via EEG and is seen to be a strong indicator of emotional states. Specifically, approach and withdrawal motivation which have been associated with positive and negative emotions respectively. Using a combination of behavioural and physiological methods in measuring preference and responses gives us an accurate representation of the participant responses. In this study, three tests were conducted during a continuous EEG recording. Test 1: The implication of inducing a positive mood before the onset of stimulus line-up and the extent of its effect on emotions and alpha asymmetry is not extensively studied. In this test, we employed the use of an instrumental soundscape for one experimental group before beginning the stimulus presentation to test this effect against a ‘silent’ control group. Test 2: This test aims to compare the participants’ physiological measures (EEG) and behavioural self-reports to audio advertisement stimuli consisting of different categories of music: ‘Brand music’ vs. ‘Campaign’ music or ‘No music’ Controls. Test 3: There is ambiguity in research regarding how frontal alpha asymmetry as measured by EEG and self-report preferences might change with changing the format of the advertisement to: only Audio, Audiovisual and Silent videos. There has been contradictory evidence regarding the impact of music on an individual’s emotions and consequent memory and decision-making. This thesis delves into these questions through the post-study behavioural test and simple binary choice paradigm that measure the above-mentioned in relation with the stimuli presented to participants. Our results did not show a significant difference in frontal asymmetry in the stimulus presentation across the three tests conducted during EEG recording. The behavioural data however indicated significant preference in behavioural self-report ratings for Brand Music- associated stimuli in Test 2 and for Audiovisual advertisement stimuli in Test 3. Results also revealed a significant correlation between ratings given to a stimulus and post-study memorability. The final binary choice paradigm test indicated higher preference to products related to stimulus presentation (‘advertised’ brand) vs similar products not related to the presented stimulus (‘non-advertised’ brand). We anticipate that these results will further help us understand and predict general preferences that can help companies, government policy-makers and the general public be more aware and better equipped to manage their valuable resources of money, time, attention and memory.
  • Rooney, Erin Jane (2022)
    Meningeal lymphatic vessels (mLVs), a recent functionally characterized structure in the meninges, contribute to the clearance of macromolecules, immune cells and metabolic waste from the central nervous system to peripheral lymph nodes. Having been identified as a route of clearance, there is a focus on understanding their role in neurological disease pathology. Here we consider their function in the pathology of traumatic brain injury (TBI) particularly in blood solute clearance, lesion progression and neuroinflammatory response. We use a transgenic model of mLV developmental dysfunction, K14-VEGFR3-Ig, to analyze the progression and severity of a controlled cortical impact (CCI) injury. We show that in mice lacking mLVs there are a higher percentage of microglia cells in an activated state in the hippocampus whereas the progression of hematoma and lesion size does not differ from wild type. Our results suggest that at two months post injury, meningeal lymphatics could be functionally important in modulating microglia activation, which is associated with chronic inflammation.
  • Verle, Maarten (2021)
    Advancements in both calcium indicators and optical instrumentation have led to new in vivo techniques, such as Miniscopes, capable of recording the spatiotemporal activity of multiple neurons during unrestrained behaviour in rodents. With these microendoscopic techniques, neuronal populations can be stably recorded over multiple sessions. As a result, Miniscopes allow for the investigation of a brain region’s changing activity patterns as a result of disease progression or behaviour. Recently, open source Miniscope initiatives have led to affordable and accessible versions of this technique. In addition, the collaborative open-source community facilitates rapidly evolving modifications, implementations and designs. Notwithstanding the potential and ever-increasing popularity of Miniscopes, the technique is still in its infancy and not widespread. This study consisted of a background review and a pilot study attempting to image neuronal ensembles in the central nucleus of the amygdala (CeA) using the open-source UCLA V3 Miniscope in mice. Despite not being able to successfully record neuronal activity in the CeA, the study has made progress in generating a protocol for Miniscope implementation at the Pharmacology department of Helsinki. Moreover, the study proposes different adjustments that might be implemented in the future. With the continuation of a synergistic collaboration with the Department of Psychology at the university of Jyväskylä, it is likely that both departments will be able to effectively implement the Miniscope technique in the foreseeable future.
  • Acosta Leinonen, Johanna Natalia (2019)
    Sleep is one of the most vital functions of newborns and infants, and it is essential for neuronal network development. Therefore, long-term sleep disturbances have been associated with growth delays and behavioral disorders. Commonly reported infant sleep disturbances, such as night awakenings and difficulties falling asleep, cause distress to parents. Yet, the development of infant sleep in the home environment has not been fully elucidated due to lack of objective measurement parameters. In the current study, we assessed the feasibility of a motion sensor, attached to wearable pants, and ECG textile electrodes to monitor sleep-related respiration and heart rate of newborns and infants. First, we compared signals recorded by the motion sensor’s measurement channels to the standard respiratory piezo effort belt’s signal during daytime EEG recordings. According to our results, the motion sensor’s gyroscope proved to measure respiratory rate most accurately, while the ECG signal transmitted by the sensor was reliable in interpretable sections. We then provided wearable garments and smartphones to families with infants to assess overnight home-use. Our results indicate that different sleep states could likely be identified based on respiration fluctuation visible in the gyroscope’s signals. Moreover, the wearable system was considered practical and easy to use by the parents. Future studies should focus on validating the sensor with clinically approved measures, in order to train the algorithms to automatically identify different sleep-wake states. By doing so, the wearable sensor could provide information on natural infant sleep structure development over long time periods. Additionally, clinical validation of the sensor may result in the development of a companion diagnostic tool for infant cardiorespiratory and movement disorders.
  • Kurkinen, Karoliina (2019)
    Semantics is a study of meaning in language and basis for language comprehension. How these phenomena are processed in the brain is still unclear especially in naturalistic context. In this study, naturalistic language comprehension, and how semantic processing in a narrative context is reflected in brain activity were investigated. Subjects were measured with functional magnetic resonance imaging (fMRI) while listening to a narrative. The semantic content of the narrative was modelled computationally with word2vec and compared to voxel-wise blood-oxygen-level dependent (BOLD) brain signal time courses using ridge regression. This approach provides a novel way to extract more detailed information from the brain data based on semantic content of the stimulus. Inter-subject correlation (ISC) of voxel-wise BOLD signals alone showed both hemispheres taking part in language comprehension. Areas involved in this task overlapped with networks of mentalisation, memory and attention suggesting comprehension requiring other modalities of cognition for its function. Ridge regression suggested cerebellum, superior, middle and medial frontal, inferior and medial parietal and visual cortices bilaterally and temporal cortex on right hemisphere having a role in semantic processing of the narrative. As similar results have been found in previous research on semantics, word2vec appears to model semantics sufficiently and is an applicable tool in brain research. This study suggests contextual language recruiting brain areas in both hemispheres and semantic processing showing as distributed activity on the cortex. This activity is likely dependent on the content of language, but further studies are required to distinguish how strongly brain activity is affected by different semantic contents.
  • Lepistö, Santeri (2023)
    Efficient processing of auditory information begins to emerge early in human ontogeny and establishes foundations for learning language from speech exposure. Here we show that repeated exposure to spoken words causes in neonatal brain attenuated neural responses that are linked to language skills at the age of 24 months. In the study, 75 newborn infants were exposed to repeated presentation of two spoken disyllabic pseudowords. During the word exposure, event-related potentials to presented pseudowords were measured with electroencephalography. The study provides three kinds of findings regarding neonatal brain dynamics and repetitive word exposure. Firstly, the results show that continuous exposure to spoken pseudowords modulates neonatal brain activity and can lead to attenuation of neural responses. This neural suppression likely reflects neonates’ early capacity to recognize spoken words and form neural representations of the stimuli through repetition. Secondly, the attenuated neural responses were bound to the presentation of the first syllable and did not occur after presentation of the second syllable. Thirdly, occurrence of neonatal neural suppression was associated with better expressive language skills later, at the age of 2 years. Altogether, the results provide preliminary evidence that neonatal brain responses to word repetition can be utilized to indicate efficiency of learning language from speech exposure and later state of language development.
  • Kalyanaraman, Shringaa (2024)
    Schizophrenia, a mental disorder affecting over 1% of the world’s population, has a 41-65% chance of being acquired in monozygotic twins, and shows a complex heritable pattern. Research has shown the involvement of various neuronal and glial cell types in the disorder’s progression. Recent studies are focusing on cortical interneurons, as clinical features of schizophrenia such as working memory deficits emerge due to the abnormal activity of these cells . The advent of induced pluripotent stem cell (iPSC) technology has made it easier to study schizophrenia disease mechanisms, with studies revealing differences in morphological and physiological properties of cortical interneurons in patients with schizophrenia. In this thesis , the aim was to optimize iPSC-interneuron differentiation protocol and live-cell imaging method suitable for disease modelling. Interneurons were differentiated from iPSCs with overexpression of inducible transcription factor, Achaete-scute homolog 1 (ASCL1). The iPSCs were derived from twin pairs discordant for schizophrenia and from healthy controls. Expression of interneuron-specific markers was verified using RT-qPCR and validated at the protein level by an immunocytochemistry (ICC) assay in the control cell lines first. Additionally, to estimate the formation of neurites and differences in neurite length and branching, the differentiated interneurons from the controls were subjected to live-cell imaging by IncuCyte S3 live-cell imaging system. Imaging parameters such as cell body cluster filter was optimized to visualize the neurites. To study interneuron involvement in schizophrenia, iPSCs from one twin pair discordant for schizophrenia were successfully differentiated. Interneurons strongly expressed Gamma-aminobutyric acid (GABA) neurotransmitter related neuronal markers: glutamate decarboxylase 67 (GAD67) and GABA at protein level. The neurons were identified as somatostatin (SST) subtype GABAergic neurons by their mRNA and protein expression. While it was possible to observe differences in gene expression, there were no clear differences in the morphology of the differentiated cells as well as the localization of markers in comparison to the healthy controls. Further studies should focus on having a protracted time for differentiation where more mature interneurons can be produced by establishing co-cultures with excitatory neurons. This will help replicate the in vivo cortical machinery which in turn will aid in better understanding of disease mechanisms.