Browsing by Subject "cerebellum"
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(2023)Morphological features are considered as markers of microglial functionality, and they show regional heterogeneity in the brain. Recently the sleep-wake cycle was shown to affect microglial morphology in mice and correlate with cortical sleep slow wave activity (SWA). Microglial sizes and ramification increased during the dark period and decreased during the light period in cerebral areas associated with SWA, suggesting that neuronal activation could be affecting microglial morphology through SWA. I studied microglia in the hindbrain areas with and without functional connection to SWA to further investigate the association between SWA and alterations in morphology, and to investigate if there are differences in microglial morphology and their diurnal alterations in brain regions other than those commonly investigated. I examined three hindbrain areas (cerebellar cortex (CC), deep cerebellar nucleus (DCN) and medial vestibular nucleus (MVN)) and somatosensory cortex (SC) of mice (n=15) at two timepoints: 6 hours after the light onset (high SWA) and offset (low SWA). My aims were to answer if there are morphological differences in microglia between 1) the four brain areas at both timepoints and 2) between the two timepoints in each brain area. My hypotheses were that CC and DCN which have functional connections to cortical SWA, would show similar diurnal morphology alterations as demonstrated in the cerebral areas, and MVN that has no known cortical SWA connection, would lack significant alterations. As microglia are heterogenous throughout brain, I expected microglia to differ between different brain areas, especially the hindbrain and the SC. I found that microglial morphologies significantly differed between the hindbrain and the cortex, while the hindbrain areas were more similar in morphology. Moreover, the brain areas demonstrated diurnal morphology alterations of microglia with varying extent: CC and DCN microglial morphology did not correlate with SWA as clearly as SC did, and interestingly, morphological features of MVN microglia showed a pattern opposite to other areas, microglia being larger during the light period than the dark period. These results highlight the importance of the diurnal time to microglial morphology and the heterogeneity of microglia between different brain regions.
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(2018)Kainate receptors (KARs) are glutamate receptors that modulate neurotransmission and neuronal excitability. They assemble from five subunits (GRIK1-5 or GluK1-5) present at both pre- and postsynaptic membranes. KAR function is regulated by neuropilin and tolloid-like (NETO) proteins, which also regulate postsynaptic GRIK2 abundance. Some KAR subunit gene variants associate with psychiatric disorders. Moreover, Grik1, Grik2 and Grik4 knock-out (KO) mice display changes in anxiety- and fear-related behaviours. In previous work, Neto2 KO mice expressed higher fear and impaired fear extinction in the fear conditioning paradigm. We hypothesised that this phenotype could be due to reduced KAR subunit abundance in fear-related brain regions, i.e. ventral hippocampus, amygdala and medial prefrontal cortex (mPFC). We specifically investigated GRIK2/3 and GRIK5 levels in the subcellular synaptosomal (SYN) fraction using western blot. We did not observe any difference between genotypes in any of the brain regions. However, our statistical power may have been insufficient, particularly for amygdala and mPFC. Also, an effect on synaptic KAR subunit abundance might be specific to either pre- or postsynaptic compartment, and thus more difficult to detect in SYN fractions. Alternatively, NETO2 absence may affect KAR actions instead of their subunit levels in fear-related brain regions, which could be examined through electrophysiological recordings. Ultimately, unravelling how a molecular system without NETO2 gives rise to fear behaviour in mice may lead to a better understanding of fear-related disorders in human and to new therapeutic strategies.
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