New Transgenic Mouseline Reveals Mechanism for Outer-to-Inner Hair Cell Transitions
Zhenghong Bi, Minhui Ren, Yu Zhang, Shunji He, Lei Song et al.
(see article e1751232024)
Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) are critical for our ability to hear and our perception of sound. It is estimated that 90% of genetic hearing loss is caused by problems with hair cells. Exploring mechanisms of hair cell development is important for developing treatment strategies for hair cell regeneration. Tbx2 is expressed in IHCs but is dampened in OHCs. OHCs with Tbx2 are thought to convert into IHC-like cells, but how rampantly this occurs and the mechanisms underlying this conversion are unknown. Bi and colleagues used a new mouse model to overexpress Tbx2 in cochlear sensory progenitors, neonatal OHCs, or adult OHCs in vivo. They found that Tbx2 overexpression in neither neonatal OHCs nor cochlear progenitors led to complete transitions into IHCs. Lastly, restoring an OHC gene that was downregulated following Tbx2 overexpression (Ikzf2) minimized abnormal OHC formation. Thus, OHCs that do transition into IHC-like cells may do so via a repression of Ikzf2. These are informative findings for researchers developing treatment strategies for hair cell regeneration.
Merged images of outer (top) and inner (bottom) hair cells labeled for Myo7a (green), tdTomato (red), and HA (Tbx2, white) in an Atoh1-Tbx2 mouse. Orange arrow points to a cell expressing all fluorescent labels. Assessing these images contributed to the finding that Tbx2 misexpression converts cochlear progenitor cells into IHC-like cells with disorganized hair bundles. See Bi et al. for more details.
ACC Tracking of Context-Dependent Behaviors
Adrian J. Lindsay, Isabella Gallello, Barak F. Caracheo, and Jeremy K. Seamans
(see article e1670232024)
Contexts and emotional states shape many of our behaviors. There is strong evidence for the anterior cingulate cortex (ACC), which processes information on emotional and autonomic states and the behaviors they play roles in, as a regulator of context-dependent behaviors. Herein, Lindsay et al. push the needle forward in our understanding of how ACC-driven behaviors are modified by different emotional states. They exposed male rats to contexts stimulating different emotional responses (experimental sessions conditioning rats to associate a tone with either food, a foot shock, or no outcome) while recording from ACC neuron ensembles and characterizing distinct behaviors across sessions with their newly developed machine learning pipeline. The authors found that the ACC tracked both individual behaviors and emotional contexts. Very few neural representations of behavior were the same across contexts, and changes in behavioral sequences did not account for these context-dependent neural representations of behavior. While sex differences remain unexplored, these findings are a breakthrough in our understanding of how the ACC processes and tracks emotional states to drive context-dependent behaviors.
Footnotes
This Week in The Journal was written by Paige McKeon
