Functional Development and Plasticity of Parvalbumin Cells in Visual Cortex: Role of Thalamocortical Input
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CitationQuast, Kathleen Beth. 2012. Functional Development and Plasticity of Parvalbumin Cells in Visual Cortex: Role of Thalamocortical Input. Doctoral dissertation, Harvard University.
AbstractUnlike principal excitatory neurons, cortical interneurons comprise a diverse group of distinct subtypes. They can be classified by their morphology, molecular content, developmental origins, electrophysiological properties and specific connectivity patterns. The parvalbumin-positive \((PV^+)\), large basket interneuron has been implicated in two cortical functions: 1) the control and shaping of the excitatory response, and 2) the initiation of critical periods for plasticity. Disruptions in both phenomena have been implicated in the etiology of cognitive developmental disorders. Careful characterization of \(PV^+\) cell function and plasticity in response to their primary afferent, the thalamocortical synapse, is needed to directly relate their vital contribution at a synapse-specific or network level to whole animal behavior. Here, I used electrophysiological, anatomical and molecular genetic techniques in a novel slice preparation to elucidate \(PV^+\) circuit development and plasticity in mouse visual cortex.
I found that GFP-positive \(PV^+\) cells in layer 4 undergo a rapid maturation after eye opening just prior to onset of the critical period. This development occurs across a number of intrinsic physiological properties that shape their precise, fast spiking. I further optimized and characterized a visual thalamocortical slice to examine the primary afferent input onto both pyramidal and \(PV^+\) cells. Thalamic input onto \(PV^+\) cells is larger, faster and again matures ahead of the critical period. Both the intrinsic and synaptic properties of \(PV^+\) cells are then maintained by a secreted homeoprotein, Otx2 (Sugiyama et al, 2008), which is mediated by an extracellular glycosaminoglycan recognition. Since the plasticity of fast-spiking, inhibitory neurons is dramatically distinct from their neighboring pyramidal neurons in vivo (Yazaki-Sugiyama et al. 2009), I directly examined the plasticity of thalamocortical synapses in vitro. After brief monocular deprivation, thalamic input specifically onto \(PV^+\) cells is reduced while remaining unaltered in pyramidal cells. Deprivations prior to critical period onset or in GAD65 knockout mice neither produce a shift of visual responsiveness in vivo (Hensch et al, 1998) nor reduce thalamocortical input onto \(PV^+\) cells. These results directly confirm that \(PV^+\) cells are uniquely sensitive to visual experience, which may drive further rewiring of the surrounding excitatory cortical network.
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