Plasticity of interneuronal species diversity and parameter variance in neurological diseases

Interneuronal diversity reflects the division of labor between numerous highly specialized interneuronal species, each performing a set of specific functions in neuronal networks. The rich diversity of interneurons found in the normal healthy brain is often significantly altered in neurological and psychiatric diseases. In genetic and developmental disorders, the diversity of interneuronal networks is compromised because of disturbances in the generation, specification or migration of specific interneuronal subtypes. Following insults related to trauma and seizures, the relative abundance of interneuronal subtypes might change, and entire interneuronal species can be lost from the network. In addition to the complete or partial loss of interneuronal subgroups, heterogeneity can also be altered in more subtle ways, as a result of changes in cell-to-cell variance of a particular parameter within specific interneuronal populations. Computational and experimental studies show that alterations in cellular and synaptic GABAergic heterogeneity can significantly modulate both firing rates and network coherence, indicating that plasticity of interneuronal diversity is likely to be an important mechanistic component of malfunctioning cortical networks in many pathological states.