PT  - JOURNAL ARTICLE
AU  - Diankun Yu
AU  - Matthieu Maroteaux
AU  - Yingnan Song
AU  - Xiao Han
AU  - Isabella Febbo
AU  - Claire Namboodri
AU  - Cheng Sun
AU  - Wenduo Ye
AU  - Emily Meyer
AU  - Stuart Rowe
AU  - YP Chen
AU  - LA Schrader
TI  - The transcription factor Shox2 shapes thalamocortical neuron firing properties by regulation of key ion channels
AID  - 10.1101/660662
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 660662
4099  - http://biorxiv.org/content/early/2019/06/05/660662.short
4100  - http://biorxiv.org/content/early/2019/06/05/660662.full
AB  - Thalamocortical neurons (TCNs) transmit information about sensory stimuli from the thalamus to the cortex and are capable of tonic and phasic burst firing modes in response to different physiological states. These firing properties of TCNs are supported by precisely-timed inhibitory synaptic inputs from the thalamic reticular nucleus and intrinsic T-type Ca2+ and HCN currents. These intrinsic currents are mediated by Cav3.1 and HCN channel subunits, and alterations in expression or these channels can have dramatic implications on thalamus function. The factors that modulate these currents controlling the firing patterns important for integration of the sensory stimuli and the consequences resulting from the disruption of these firing patterns are not well understood. Shox2 is a transcription factor important for pacemaker activity in the heart that is also expressed in adult mouse thalamus. We hypothesized that genes regulated by Shox2’s transcriptional activity may be important for firing properties of TCNs. In this study, we used RNA sequencing on control and Shox2 knockout mice to determine Shox2-affected genes and revealed a network of ion channel genes important for neuronal firing properties. Quantitative PCR confirmed that expression of Hcn2, 4 and Cav3.1 genes were affected by Shox2 KO. Western blotting showed expression of the proteins for these channels was decreased in the thalamus, and electrophysiological recordings showed that Shox2 KO impacted the firing properties of a subpopulation of TCNs. Finally, behavioral studies revealed that Shox2 expression in TCNs play a role in somatosensory function and object memory. Overall, these results reveal Shox2 as a transcription factor important for TCN function.