Mental illness is increasingly believed to be caused by malfunctioning circuitry in the brain. In newly published research led by Michael M. Halassa, M.D., Ph.D., a 2012 NARSAD Young Investigator Grantee, discoveries about how networks of cells in the healthy brain are activated/inactivated during sleep versus an awake and alert state offer insight into how external reality is effectively differentiated from internal thought processes. This process is known to be disrupted in autism spectrum disorder (ASD) and schizophrenia; the cause of the disruption has been poorly understood.
Thanks to the ongoing development of new technologies to study the brain in action, Dr. Halassa and team at NYU Langone Medical Center were able to trace two fundamentally distinct networks of inhibitory neurons in a brain structure called the thalamus. Their findings were published August 14th in the journal Cell.
The thalamus is a centrally positioned “gateway” to the cerebral cortex, which is the seat of higher brain functions, including cognition. The team’s discoveries concern the organization of neurons forming a thin layer covering the thalamus, called the thalamic reticular nucleus, or TRN. In experiments with mice, they found that the TRN performs a “switchboard”-like role, helping to direct sensory signals from the “outside” as well as internally-generated data like memories from the “inside” to their appropriate destinations in the brain.
“We’ve never been able to observe how this structure worked before,” Dr. Halassa says. “Our study shows how information can be routed, giving us tremendous insight into how it might be broken in certain disorders.”
The team identified two functional subgroups of TRN neurons, which work in opposite ways depending on whether a mouse (or by presumed extension, a person) is awake or asleep. One set of neurons, connected to sensory systems, were found to be active during sleep, effectively suppressing inputs from the senses. Greater activity was seen during periods of sleep when brief bursts of fast-cycling brain waves called spindles occur. Spindles are known to filter out sensory information—sounds, for example—and are seen less frequently in brain-wave measurements of people with ASD and schizophrenia. These neurons were less active when the mice were attentive.
The researchers then discovered that a second set of TRN neurons, wired to internal information processing, were inactive during sleep. This may be important for how memories are formed during sleep, Dr. Halassa reports. These neurons were active when the animals were awake and performing a task.
The researchers believe that this new work may identify the underlying circuitry that gets disrupted in ASD and schizophrenia, impeding the appropriate flow and suppression of information through the thalamic “switchboard” and disabling the distinction between external reality and internal thought processes. Dr. Halassa hopes the study will ultimately support the development of newly targeted treatments for these symptoms of ASD and schizophrenia.
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