145 The MAOA promoter methylation was decreased in females with depression or panic disorder compared with controls.146,147 Finally, among serotonin receptors, increased 5-HT3A receptor methylation in the promoter region was associated with alcohol exposure in humans148 and mice.149 More studies are necessary to determine the impact of early-life stress on these novel serotonin-related epigenetic targets. Serotonin and the reinstatement of juvenile forms of plasticity Early-life experiences permanently shape neural circuit wiring and function during critical time periods of development.150 In mammals, monocular deprivation during the juvenile critical time FK228 purchase period leads to permanent Inhibitors,research,lifescience,medical changes in the
wiring of the visual cortex, which leads to amblyopia in
the deprived eye. Chronic administration of the SSRI fluoxetine Inhibitors,research,lifescience,medical in adulthood has been shown to reinstate a form of critical time period plasticity in the visual cortex.151 Reinstatement of this type of juvenile-like plasticity promoted the recovery of visual function in amblyopic animals that had been visually deprived during the juvenile period.151 Positive effects Inhibitors,research,lifescience,medical of fluoxetine on the recovery of visual function were blocked by cortical administration of diazepam, indicating that increased cortical excitation is necessary to mediate the rejuvenating effects of fluoxetine. The mechanisms that underlie these effects were dependent on 5-HT1A receptor-dependent serotonin and brain-derived neurotrophic Inhibitors,research,lifescience,medical factor signaling and were involved in downstream epigenetic changes.152 Environmental enrichment in adulthood has also been shown to reactivate juvenile-like plasticity in the visual cortex. Rejuvenating effects of environmental enrichment on visual plasticity were also dependent on the activation of serotonin signaling pathways.153 In other systems, a critical time period for fear memory erasure was described in juvenile mice.154 During this critical time
period, which occurs before postnatal day 16 in mice, extinction training followed by an initial phase of fear conditioning Inhibitors,research,lifescience,medical led to a permanent erasure of the fear memory.154 The closure of this juvenile plasticity period depends on increased formation of perineuronal nets surrounding a specific subtype of parvalbumin-expressing interneurons in the SB505124 mw basolateral amygdala. Following the closure of this critical time period, fear conditioning induces an enduring memory that cannot be erased through extinction training.154 Recent data indicates that the combined administration of fluoxetine with extinction learning has the ability to reactivate critical period-like plasticity in the basolateral amygdala by decreasing the percentage of parvalbumin-expressing interneurons surrounded by perineuronal nets.155 Reinstatement of this critical time period-like plasticity in the basolateral amygdala of adult animals led to an erasure of the fear memory similarly to what is observed in juvenile animals.