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Targeting the excitability of motoneuron’s in ALS  

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which patients lose motor functions due to progressive loss of motor neurons in the cortex, brainstem and spinal cord. Evidence from patients in the clinic suggests that prior to the presentation of clinical symptoms, familial and sporadic ALS patients display an increase in neuronal hyperexcitability, however, the factors that instigate the changes in neural conductivity over the course of disease onset and progression are not well understood. In this project, we aim to investigate the ionic mechanisms governing changes in neuronal excitability in motor neurons of mice model for ALS. 

 Astrocytic modulation of brain waves 

Brain waves are rhythmic voltage oscillations emerging from the synchronization of individual neurons into a neuronal network. These oscillations emerge in all brain regions, and their patterns of synchrony and coherence underlie the neural code for sensory representation and short-term memory. Network oscillations range from slow to fast fluctuations and are classified by power and frequency band, with different frequency bands being associated with specific behaviours, including attention, sleep, and memory. Cortical networks are constantly alternating between different dynamic states to accommodate the large rhythmic patterns underlying the diverse cognitive functions administrated by the cortex. However, the full extent of the functional structure of these networks, especially the interactions with astrocytic networks is poorly understood. It has been postulated that at least ten distinct mechanisms are required to cover the wide frequency range of neural oscillations, however, the mechanisms that gear the transition between distinct oscillatory frequencies are unknown. In this study, we aim to discover the involvement of astrocytes, the prevailing subtype of glia in the brain, in modulating network activity. Specifically, we focus on astrocytic K+ clearance processes in modulating neural oscillations at both network and cellular levels. Since astrocytes are central for maintaining K+homeostasis, our study suggests that modulation of their inherent capabilities to clear K+ from the extracellular milieu is a potential mechanism to optimize neural resonance behaviour and thus tune neural oscillations.

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  The impact of neuroinflammation on Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by significant impairment of cognitive function, memory loss and behavioural phenotypes such as anxiety and depression. There are several hypotheses regarding the etiology of AD. The first and oldest hypothesis is the "cholinergic hypothesis" which suggests that a serious loss of cholinergic function in the basal forebrain and the associated loss of cholinergic innervation in the hippocampus and neocortex contribute significantly to the cognitive symptoms associated with AD. However, the main cause underlying the loss of cholinergic cells is still unknown. Recent findings suggest that neuroinflammation is a preliminary process, which plays a role in the onset of Alzheimer’s disease. However, the impact of neuroinflammation on cholinergic neurons is still an undiscovered area. In this project, we aim to determine the effects of chronic and acute inflammatory processes on neurophysiological properties of the basal forebrain cholinergic system, and the susceptibility of cholinergic neurons during aging. 

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