Researchers at Case Western Reserve University School of Medicine have created the first complete model to describe the role that serotonin plays in brain development and structure. Serotonin, also called 5-hydroxytryptamine [5-HT], is an important neuromodulator of brain development and the structure and function of neuronal (nerve cell) circuits. The results were published in the current issue of The Journal of Neurophysiology online.
“Our goal in the project was to close the gap in knowledge that exists on role of serotonin in the brain cortex, particularly as it concerns brain circuitry, its electrical activity and function,” said Roberto Fernández Galán, PhD, Assistant Professor in the Department of Neurosciences at Case Western Reserve University School of Medicine. “For the first time, we can provide a complete description of an animal model from genes to behavior–including at the level of neuronal network activity, which has been ignored in most studies to date.”
Dr. Galán and his team used high-density multi-electrode arrays in a mouse model of serotonin deficiency to record and analyze neuronal activity. The study supports the importance of the serotonin which is specified and maintained by a specific gene, the Pet-1 gene – for normal functioning of the neurons, synapses and networks in the cortex, as well as proper development of brain circuitry. Serotonin abnormalities have been linked to autism and epilepsy, depression and anxiety. By more fully elucidating the role of serotonin in the brain, this study may contribute to a better understanding of the development or treatment of these conditions.
“By looking at the circuit level of the brain, we now have new insight into how the brain becomes wired and sensitive to changing serotonin levels.” added Dr. Galán.
In addition to Dr. Galán, who served as senior author of the study, former graduate student, Pavel A. Puzerey, and undergraduate student majoring in Physics, Nathan X. Kodama, contributed to this project.
Funding: Dr. Galán’s research is funded with a Biomedical Researcher Award from The Hartwell Foundation.
Source: Marc Kaplan – Case Western Reserve University
Image Credit: The image is credited to Ben Mills and is in the public domain
Original Research: Abstract for “Abnormal cell-intrinsic and network excitability in the neocortex of serotonin-deficient Pet-1 knock-out mice” by Pavel Anatolyevich Puzerey, Nathan Xing Kodama, and Roberto Fernandez Galan in Journal of Neurophysiology. Published online November 25 2015 doi:10.1152/jn.00996.2014
Abstract
Abnormal cell-intrinsic and network excitability in the neocortex of serotonin-deficient Pet-1 knock-out mice
Neurons originating from the raphe nuclei of the brainstem are the exclusive source of serotonin (5-HT) to the cortex. Their serotonergic phenotype is specified by the transcriptional regulator Pet-1, which is also necessary for maintaining their neurotransmitter identity across development. Transgenic mice in which Pet-1 is genetically ablated (Pet-1-/-) show a dramatic reduction (~80%) in forebrain 5-HT levels, yet no investigations have been carried out to assess the impact of such severe 5-HT depletion on the function of target cortical neurons. Using whole-cell patch clamp methods, 2-D multielectrode arrays (MEA), 3-D morphological neuronal reconstructions, and animal behavior, we investigated the impact of 5-HT depletion on cortical cell-intrinsic and network excitability. We found significant changes in several parameters of cell-intrinsic excitability in cortical pyramidal cells (PC), as well as an increase in spontaneous synaptic excitation through 5-HT3 receptors. These changes are associated with increased local network excitability and oscillatory activity in a 5-HT2 receptor-dependent manner, consistent with previously reported hypersensitivity of cortical 5-HT2 receptors. PC morphology was also altered with a significant reduction in dendritic complexity which may possibly act as a compensatory mechanism for increased excitability. Consistent with this interpretation, when we carried out experiments with convulsant-induced seizures to asses cortical excitability in vivo, we observed no significant differences in seizure parameters between wild-type and Pet-1-/- mice. Moreover, MEA recordings of propagating field potentials showed diminished propagation of activity across the cortical sheath. Altogether these findings reveal novel functional changes in neuronal and cortical excitability in mice lacking Pet-1.
“Abnormal cell-intrinsic and network excitability in the neocortex of serotonin-deficient Pet-1 knock-out mice” by Pavel Anatolyevich Puzerey, Nathan Xing Kodama, and Roberto Fernandez Galan in Journal of Neurophysiology. Published online November 25 2015 doi:10.1152/jn.00996.2014
