A Pint of Edinburgh Neuroscience

How does the newborn brain go from individual cells, sending spontaneous signals, to complex connected networks capable of fast and subtle information processing? Here, I will present a project investigating how Fragile X Syndrome, an Autism Spectrum Disorder, can be used to probe the process of development, and the mechanisms that keep that development in balance. Using whole-cortex calcium imaging, we look at ways of measuring information complexity, and potentially identifying critical periods of divergence in developing brains.

Suicidal attempts with pesticides costs about 300,000 lives annually across the world. Clinical manifestation include; acute cholinergic syndrome, delayed intermediate syndrome (IMS) and chronic neuropathies. Acute cholinergic syndrome is well characterized and respond well to the antidote treatments (oximes), however IMS was not well understood. IMS has a delayed onset with partial or complete paralysis of upper body muscles including respiration muscles. These patients need mechanical ventilation lasting from days to weeks until they regain respiration spontaneously. Mechanisms of this muscle paralysis is unknown and yet, no specific treatments available. Therefore I have investigated the neuromuscular junction (NMJ) transmission failure using specific organophosphorus pesticide; dimethoate EC40. I have found that metabolic breakdown products of this pesticide are more potent compared to its parent compounds (active ingredient/ dimethoate and solvent/cyclohexanone). Combinatorial effects of those metabolites are mainly responsible for the delayed NMJ transmission failure. Studies carried out in in-vivo pig model of pesticide poisoning, also shown possible treatment options to overcome muscle paralysis.

Autism spectrum disorders (ASD) are characterized by social impairments and restricted behaviours. To investigate how changes in brain activation mediate behaviour in ASD, we use rodent models of ASD, such as Fragile-X knockout (Fmr1-/y). To identify neurons in the rat brain that are activated during fear, we used the immediate-early gene cFos as a proxy for neuronal activation and combined this with optical clearing and light-sheet microscopy.