Summary: Newly identified neurons in the reticular thalamus could help shed light on the link between seizures and psychiatric disorders such as ADHD and schizophrenia, a new study reports.
Source: Gladstone Institute.
Cells related to seizures, schizophrenia, and ADHD all found in the same region of the brain.
In a new study published in Cell Reports, scientists at the Gladstone Institutes identified different types of neurons in a brain region called the reticular thalamus. A better understanding of these cells could eventually help explain how both seizures and certain psychiatric disorders can occur at the same time.
Most sensory information from the outside world–including sight, touch and sound–is collected in a region of the brain called the thalamus. The thalamus then relays signals to the cerebral cortex, the brain’s outermost layer responsible for higher processes like decision-making.
“The reticular thalamus acts like a gate that filters information from the thalamus and dispatches signals to the cortex,” explained Jeanne Paz, PhD, assistant investigator at Gladstone and senior author of the new study. “You can think of it as a switchboard operator from the 1950s, who would transfer incoming calls to the correct parties.”
The reticular thalamus is involved in several functions, including attention, perception, and consciousness. Disruptions in this region can lead to seizures and psychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder (ADHD). However, little is known about how neurons in this brain region function as gatekeepers.
“Before our study, the reticular thalamus was thought to be composed of one type of neuron,” said Alexandra Clemente, graduate student in the Paz laboratory and first author of the study. “We did not have a firm grasp on how cells in the reticular thalamus could execute the different functions of this brain region. We have now shown in mice that the reticular thalamus contains at least two different types of neurons, each with distinctive properties, roles, and locations.”
The two main types of neurons can be differentiated, because they produce distinct proteins, either parvalbumin (PV) or somatostatin (SOM). These cell types have been extensively studied in other regions of the brain, but not in the reticular thalamus.
“Importantly, we discovered that the two types of cells control different brain functions,” said Paz, who is also an assistant professor of neurology at the University of California, San Francisco. “We found that PV cells are involved in sensation and can be targeted to control seizures. In contrast, SOM cells are involved in cognition and emotion, and dysfunctions in these cells may contribute to ADHD and schizophrenia.”
Thanks to optogenetics tools, a technology that uses light to control the activity of cells, Paz’s team was able to specifically target and study each of the different cell types in mouse models.
“Along with my lab colleagues Stefanie Makinson and Bryan Higashikubo, we designed studies to examine seizures,” added Clemente. “Our results showed that targeting PV cells could disrupt seizures, whereas targeting SOM cells had no effect. This finding reinforced the notion that, in addition to their distinct physiological functions, the two cell types have very different roles in disease.”
Through collaborative efforts, the scientists also validated, for the first time, that both PV and SOM cells exist in the human reticular thalamus.
“Now that we’ve confirmed the human relevance of our findings, our future goal is to better understand the roles of the different cell types in psychiatric and neurological disorders, and to determine if targeting these cells can actually help treat seizures,” concluded Paz. “The interaction between the two types of neurons could also help explain the presence of seizures in patients with schizophrenia, dementia and some forms of autism.”
Other Gladstone researchers who participated in the study were Scott Brovarney, Frances S. Cho, Alexander Urry, Stephanie S. Holden, and Matthew Wimer. Collaborators from Stanford University (Karl Deisseroth and Lief E. Fenno) and the Hungarian Academy of Sciences (László Acsády and Csaba Dávid) also took part in the study.
Funding: Research at Gladstone was supported by the NIH (National Institute of Neurological Disorders and Stroke; grants R00NS078118 and R01NS096369), the Gladstone Institutes, the Kavli Institute for Fundamental Neuroscience, the ILAE Michael Prize, the Department of Defense (grant EP150038), the National Science Foundation (grants 1608236, 1650113, 1144247), the Weill Foundation, the American Epilepsy Society, and the Dravet Syndrome Foundation.
Source: Julie Langelier – Gladstone Institute
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms” by Alexandra Clemente-Perez, Stefanie Ritter Makinson, Bryan Higashikubo, Scott Brovarney, Frances S. Cho, Alexander Urry, Stephanie S. Holden, Matthew Wimer, Csaba Dávid, Lief E. Fenno, László Acsády, Karl Deisseroth, and Jeanne T. Paz in Cell Reports. Published online June 6 2017 doi:10.1016/j.celrep.2017.05.044
Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms
•nRT PV, but not SOM, neurons exhibit intrinsic rhythmogenic properties
•nRT PV and SOM neurons segregate into separate thalamocortical circuits
•nRT PV and SOM neurons differentially modulate oscillations in somatosensory cortex
•nRT PV cells are preferentially engaged in somatosensory behavior and seizures
Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV) and somatostatin (SOM) expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms.
“Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms” by Alexandra Clemente-Perez, Stefanie Ritter Makinson, Bryan Higashikubo, Scott Brovarney, Frances S. Cho, Alexander Urry, Stephanie S. Holden, Matthew Wimer, Csaba Dávid, Lief E. Fenno, László Acsády, Karl Deisseroth, and Jeanne T. Paz in Cell Reports. Published online June 6 2017 doi:10.1016/j.celrep.2017.05.044