Turning On the Off Switch

The role of thalamocoritcally expressed Shox2 in guiding proper development of inhibitory interneurons in the barrel cortex

Abstract

In the thalamocortical circuit, cortical inhibition is important for fine-tuning the cortical activity of the adult mouse brain. Incomplete or improper development of cortical inhibitory interneurons is associated with disorders such as epilepsy and autism. Cortical interneurons are mainly located throughout the cortical layers of the primary somatosensory cortex (S1). The somatosensory cortex receives direct input from the thalamus indiscrete regions known as “barrels”. Each barrel contains a diverse collection of neurons that receive input specific to an individual vibrissa. The ability to visualize the barrel cortex upon immunological staining techniques makes the barrel cortex a helpful tool for investigation of cortical development and plasticity.

In the present study, we will investigate the role of Shox2, a transcription factor located in thalamocortical neurons, in cortical development. Shox2 is known to regulate ion channels important for pacemaking activity in the brain, facilitating well-timed communications between the thalamus and the cortex. By modulating the firing properties and timing of inputs to the cortex, Shox2 expression may play a role in guiding the development of neurons in S1.

We used viral injections to unilaterally knockout Shox2 expression in P6 and P21 mice, and we investigated the role of Shox2 in postnatal cortical development. Interestingly, unilateral knockout of Shox2 at P6 resulted in structural abnormalities in the barrel cortex as well as reduced interneuron expression measured at adulthood. Unilateral Shox2 KO induced after P21 was not found to negatively influence barrel organization, however Shox2 KO induced after P21 resulted in interneuron expression abnormalities similar to those seen in P6 KO mice. This research provides supporting evidence for thalamocortically induced maturation of S1 and illuminates the criticality of Shox2 expression in cortical interneuron maturation.