Editor’s Pick: Investigating mechanisms for maladaptive homeostatic circuit changes

Reviewing Editor Niraj Desai, Ph.D. selected this paper and explains why he considers it noteworthy.

Homeostatic plasticity is an important feature of development. Most studies to date have emphasized its compensatory nature, helping to keep neural activity in check at times of dramatic synapse and axonal growth and changes in sensory input. But in some cases, homeostatic mechanisms may become maladaptive, especially if they cause circuits to overshoot normal activity levels. For example, prolonged periods of activity deprivation can result in lifelong seizures.

Wise et al. explored this issue using an organotypic slice culture. They demonstrated that prolonged silencing results in hypersynchronous seizure-like activity that depends on the duration of the silencing and the developmental stage at which it begins, and that circuit activity only partially recovers once the silencing is removed. These findings parallel those of earlier in vivo studies, demonstrating the usefulness of the model system. Moreover, the authors used the system to ask mechanistic questions. They found that the abnormal activity results from both an increase in intrinsic excitability and an increase in excitatory-inhibitory balance. NMDA-dependent Hebbian plasticity does not appear to be involved.

The study is exceptionally well crafted and presented; both the reviewers and the editor were struck by the quality of its argumentation. The preparation and the approach described here may well provide an important testbed for understanding pathophysiological mechanisms and exploring potential treatments.

Read the full article:

Progressive Circuit Hyperexcitability in Mouse Neocortical Slice Cultures with Increasing Duration of Activity Silencing
Derek L. Wise, Samuel B. Greene, Yasmin Escobedo-Lozoya, Stephen D. Van Hooser, and Sacha B. Nelson