Nina Karpova
Sigrid Jusélius laboratory, Neuroscience Center, University of Helsinki, Finland
Antidepressant treatments have been shown to promote different forms of neuronal plasticity, including neurogenesis, synaptogenesis, and neuronal maturation in the hippocampus. We and other laboratories have shown that antidepressants activate signaling of TrkB, the receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) in adult brain, and that BDNF-TrkB signaling appears critical for the behavioral effects of antidepressants in rodents. Neuronal plasticity is active during the early postnatal life, when neuronal networks are modified by environmental guidance, but plasticity is much more restricted in adult brain. We have shown that chronic antidepressant treatment reactivates critical period-like plasticity in the visual cortex of adult rats and, when combined with environmental manipulation, antidepressant treatment can bring about changes in the structure of visual neuronal networks. These effects were associated with increased BDNF and could be inhibited by blocking BDNF signaling through TrkB receptors, emphasizing the important role of BDNF in adult plasticity. We have recently observed that the antidepressant, fluoxetine, reactivates a developmental-like state in the fear-conditioning circuitry, including the amygdala and prefrontal cortex. Fluoxetine treatment increases BDNF expression and induces structural changes reminiscent of early postnatal period in the network comprising amygdala and prefrontal cortex. When combined with fear extinction training, these responses lead to long-term erasure of the conditioned fear response. Our data suggest that pharmacological agents, such as antidepressants, can reactivate developmental-type cortical plasticity and help to repair neuronal networks abnormally wired by adverse early experiences, when antidepressant treatment is combined with environmental rehabilitation in many parts of the cerebral cortex