GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia
Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.
Very interesting. I suppose it's the specificity that makes BL-1020 interesting because there are of course many gaba enhancing medications on the market that do absolutely nothing for schizophrenia. However, I will readily admit that the gaba system is every bit as complex as the 5HT system or any other. The proof will be in the pudding...will be exciting to see what they report. I'd like to see a new agent that has a chance to address negative symptoms. What a nightmare disease.