S 2-1-2-3 Enhancement of fear memory after retrieval

atients at highest risk for morbidity and mortality. Cognitive changes in emory, learning, attention and decision making usually occur first in the rodromal stage of schizophrenia, whereas positive and negative sympoms emerge much later. Unfortunately, due to a lack of effective treatment ptions for early cognitive symptoms, patients are usually not offered treatent until they display overt psychosis. Aberrant hippocampal neurogenesis as been demonstrated in both the brains of patients with schizophrenia and nimal models of this disease, and this process is proposed to be involved n the pathophysiology of cognitive symptoms in patients with schizophreia. We have performed an in vivo screen in search of chemicals capable f enhancing the formation of neurons in the hippocampus of adult mice, nd have discovered an aminopropyl carbazole, designated P7C3, which nhances neuron formation in the subgranular layer of the dentate gyrus. 7C3 is endowed with favorable pharmacological properties, and exerts its ro-neurogenic activity by protecting newborn neurons from apoptosis. Disuption of the gene encoding neuronal PAS domain protein 3 (NPAS3) is ssociated with cognitive dysfucntion in schizophrenia and bipolar disorder, nd mice missing this gene are devoid of hippocampal neurogenesis and dislay malformation and electrophysiological dysfunction of the dentate gyrus. e have shown that prolonged administration of P7C3 to NPAS3-deficient ice corrects these deficits by normalizing levels of apoptosis of newborn ippocampal neurons.