Over-inhibition: a model for developmental intellectual disability.
Developmental intellectual disability (DID) is a daunting societal problem. Although tremendous progress has been made in defining the genetic causes of DID, therapeutic strategies remain limited. In particular, there is a marked absence of a unified approach to treating cognitive impairments associated with DID. Here, we suggest that the brain in many DID-related disorders is subject to a basic imbalance in neuronal activity, with an increased contribution of inhibition to neural circuits. This over-inhibition, in turn, is predicted to lead to deficits in synaptic plasticity and learning and memory. We further discuss possibilities for pharmacological intervention in DID, focusing on the concept of drug-induced 'therapeutic neuroadaptation' as a means of stably enhancing constitutive circuit excitability and cognition over time.
Fernandez
Fabian
F
Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, 1201 Welch Rd, Palo Alto, CA 94304-5485, USA.
Garner
Craig C
CC
D001921:Brain / Q000503:physiopathology; D002648:Child; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics; D004777:Environment; D006801:Humans; D007266:Inhibition, Psychological; D044342:Malnutrition; D008954:Models, Biological; D009456:Neurofibromatosis 1 / Q000235:genetics; D009473:Neuronal Plasticity