Damien Zuloaga, Ph.D., a former post-doctoral fellow in the Raber lab, and colleagues at OHSU published results of a study examining the effects of methamphetamine (MA) on the sleep-wake cycle. The article, “Enhanced functional connectivity involving the ventromedial hypothalamus following methamphetamine exposure,” appearing in the 23 September, 2015, edition of Frontiers in Neuroscience, identified MA-induced alterations in coordinated activity in the brain, particularly connectivity involving the ventromedial hypothalamus (VMH). The VMH is the portion of the brain involved in satiety, thermoregulation, and fear.
MA exposure is known to both disrupt and restore circadian rhythms. Previous studies showed that sleep patterns are drastically altered almost immediately following exposure and can persist over the long term when exposure occurs during developmental phases. Other studies illustrated that the sleep rhythms in mice or rats that are arrhythmic due to damage in the portion of the brain that controls circadian cycles, the suprachiasmatic nuclei (SCN), can be regenerated with MA treatment. These findings suggested there may be an MA-sensitive Circadian Oscillator (MASCO) somewhere in the brain that is separate from the SCN. But the location and exact mechanisms were completely unknown.
To test this hypothesis, Zuloaga, Raber, and the team assessed neuronal activation in various parts of the brain following MA exposure under both day and night conditions. They found that such activation was stronger in the light phase than in the dark phase and that–interestingly–functional connectivity between the VMH and other brain areas, including other parts of the hypothalamus as well as the amygdala, was enhanced following MA exposure. These results, along with past findings that show that the VMH is involved in synchronization of circadian rhythms of circulating levels of insulin, glucose, and triglycerides, suggest a role for the VMH in the MASCO. They also suggest new ways to address the effects of MA exposure on the brain. The alterations in coordinated brain activity following MA exposure may play an important role in the substance’s deleterious effects such as anxiety, confusion, and psychotic or violent behavior.
The findings of increased activation effects during the day compared with the night also provide new information about designing studies on MA, highlighting importance of time of day as an experimental condition.
Together, these findings are an important step in unraveling the precise action MA has on the brain. They also shed light on the nature of functional connectivity to better inform assessments of neural activity patterns. Functional connectivity is an important topic of research as part of the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative, aimed at revolutionizing our understanding of the human brain and leading to new ways to treat and prevent brain disorders.
Read more about the research team their findings here.
Research team: Damian G. Zuloaga, Ph.D., Ovidu D. Iancu, Ph.D., Sydney Weber, Desiree Etzel, Tessa Marzulla, Blair Stewart, Charles N. Allen, Ph.D., Jacob Raber, Ph.D.