A study of Neural Circuitry in Microdeletion Syndrome

Sammanfattning: Abstract Introduction. The Brain is an amazingly complex piece of biological hardware, capable of massive information processing. It relies heavily on the delicate interactions between huge distributed networks to work properly. When these interactions are altered there can be any number of consequences. These carefully tuned networks are largely dependent on the internal interaction of multiple genes. When these are damaged, changes in function can be seen. For instance, the 15q-microdeletion syndrome has been implicated in the possible development of some disabling conditions, for instance schizophrenia. It has been hypothesized that a pathway between the hippocampal region and the prefrontal cortex (PFC) has altered connectivity when compared to the same pathway in non-15q-microdeletion brains. Methods. To check this hypothesis, a line of transgenic Human-15q-microdeletion mice were optogenetically modified and stimulated while recordings were taken in their PFC and stored as neuron-files, which contain data pertaining to spikes, waveform and recording location. The data acquired from acute measurements from two groups (Wild-type and Transgenic) mice was used to construct spike-time datasets. These in turn were Z-score normalized to compensate for background noise. Each neuron-unit was categorized as either an interneuron or pyramidal cell based on their firing waveform. The pyramidal cells were further divided as either excited or inhibited Pyramidal Cells. Following the classification, the datasets were classified as belonging to one of the three classes of cells. The number of each cell-class was counted within each animal genotype for population comparison. Results. The neuron raster plots revealed significant divergences in the interneuron and excited pyramidal cell response to gamma-range (40Hz) Stimulus. The Inhibited pyramidal cells exhibited what may be a deeper depression in transgenic cells, though not significant. Theta-range (6Hz) stimulus responses had no significant differences, except for inhibited pyramidal cells, which suffered a greater firing rate depression. Additionally, the ratio of cells was different between the wild-type and transgenic populations, with the transgenic mice having a reduced number of interneurons. Conclusion. Generally, the transgenic populations seem incapable of keeping up with the wild-type at gamma-range entrainment. This has been previously observed in the behavior of 15q13.3MD mice auditory neurons. Interestingly the transgenic individuals seem to have lower interneuron counts, which has been observed in some schizophrenic human patients. Lastly the KV3.1 receptor blocker seems to target transgenic neurons specifically, exhibiting no alteration of activity in wild-type neurons.