LHX2 regulates biophysical properties of astrocytes in the postnatal mouse hippocampus

The transcription factor LHX2 plays a critical role in multiple aspects of neuronal and glial development. In this study, we investigated the long-term electrophysiological consequences of Lhx2 loss in astrocytes in the CA1 region of mouse hippocampus using a genetic strategy that ensured Lhx2 was not disrupted in neurons. These mutant astrocytes exhibited a hyperpolarizing shift in their resting membrane potential, accompanied by a significant increase in input resistance and a significant decrease in input capacitance, together indicating altered biophysical properties compared with astrocytes in control mice. However, we found no significant alterations in the intrinsic electrophysiological characteristics of hippocampal CA1 neurons in mice with Lhx2 mutant astrocytes compared with controls. Collectively, we identify LHX2 as a regulator of intrinsic membrane properties of hippocampal astrocytes.NEW & NOTEWORTHY Astrocytes play a vital role in regulating neural circuit homeostasis, yet the transcriptional mechanisms governing their electrophysiological properties remain underexplored. Here, we identify the LIM-homeodomain transcription factor LHX2 as a key regulator of intrinsic electrical properties of astrocytes in the hippocampus. We demonstrate that deletion of Lhx2 from postnatal astrocytes and their progenitors alters astrocytic membrane biophysics in adulthood, but this did not have noncell-autonomous effects on the intrinsic properties of CA1 pyramidal neurons.