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Project | 02
Fragile X, the most common inherited form of autism, is a condition associated with deficits in perceptual learning. We sought to characterize experience dependent oscillations in a mouse model of Fragile X (Fmr1 KO) using a multi-faceted experimental approach. We made use of the variety of tools at our disposal such as extracellular electrophysiology in V1, visually evoked behavior analysis, cross-layer functional connectivity in V1, and channelrhodopsin-2 assisted circuit mapping (CRACM) of selected connections.
Extracellular recordings revealed impaired oscillatory activity in Fragile X mice characterized by lower amplitudes, shorter oscillation durations, and oscillation frequency shift. Functional connectivity and CRACM analysis identified altered connectivity in Fragile X mice, providing insight into the circuit level changes.
By studying experience dependent oscillations in FX mice, we have gained new insights into perceptual impairments in autism and the components of the circuits that may generate the oscillations themselves.
V1 impairments in Fmr1 KO Mice
Project | 01
Experience shapes neural activity in the brain at many scales, from the single synapses to large populations of neurons. To examine changes at the population level, we use multi-channel electrophysiology to record from primary visual cortex (V1) in awake mice. We found that repetitively presenting visual stimuli over several days profoundly changes the visually evoked responses to that stimuli. That is, before visual experience visually evoked responses are primarily stimulus locked, but afterwards they become persistent low frequency oscillations. Interestingly, these oscillations are specific to the spatial frequencies of the familiar stimulus. Our results suggest that these oscillations may represent a neural correlate of visual familiarity. Many of the efforts in this project have been focused on characterizing the fundamental properties of this oscillatory phenomenon, including oscillation duration, stimulus specificity, dynamics, and sensitivity to neuromodulation.
Oscillatory encoding of visual familiarity
Project | 03
Development of treatments for brain injuries and neurological diseases is a continuing challenge complicated by rare adult neurogenesis and poor functional recovery. A recent development which shows promise is in vivo direct NeuroD1-mediated astrocyte-to-neuron conversion. However, the mechanism of this conversion is poorly understood. To gain insight into this process, we use in vivo extracellular recordings, ex vivo channelrhodopsin-2 assisted circuit mapping, and two photon calcium imaging techniques. We seek to understand how the newly reprogrammed cells integrate into the functional neural circuit, acquire visually evoked responses, and restore function after in vivo direct reprogramming in the mouse visual cortex following focal ischemia.
Direct Reprogramming of Astrocytes into Neurons
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