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A Cellular & Network Level Investigation of Thalamocortical Neuron Oscillations & the Role of the Transcription Factor, Shox2

Thalamocortical neurons (TCNs) densely innervate the cortex and rhythmically burst fire in synchrony with cortical electrical activity that generates thalamus‐driven sleep spindles. Proper development of thalamocortical neuron cortical connectivity and firing activity underlie these sleep spindles—which are critical for memory consolidation—yet a transcriptional regulator that promotes these critical TCN characteristics has not been identified. Previously, we have shown that the transcriptional factor, Shox2, is important for the expression of key ion channels that generate TCN burst firing. Here, we have developed a targeted model using stereotactic injections of Cre virus into Shox2fl/flmice to isolate the role of Shox2 function in a single thalamic nucleus, the ventrobasal (VB) nucleus, upon TCN burst firing, cortical connectivity and organization, sleep spindles, and ultimately memory consolidation. We utilize patch clamp electrophysiology in slices to analyze burst firing of TCNs, cytochrome oxidase and VGluT2 staining of VB cortical targets (cortical barrels), in vivo electrophysiology analysis of sleep spindles, and novel object recognition to assess the effects of Shox2 KO in VB TCNs. Our findings indicate that the area under the burst curve and number of action potentials is significantly reduced, cortical barrel organization is disrupted in a P6 Shox2 KO model, sleep spindle occurrence is significantly reduced, and novel object recognition is impaired. These results show that Shox2 contributes to regulation of TCN cell properties and overall thalamic function.