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Methamphetamine regulation of activity and topology of ventral midbrain networks


Autoři: Douglas R. Miller aff001;  Joseph J. Lebowitz aff001;  Dylan T. Guenther aff001;  Alexander J. Refowich aff001;  Carissa Hansen aff001;  Andrew P. Maurer aff001;  Habibeh Khoshbouei aff001
Působiště autorů: Department of Neuroscience, University of Florida, Gainesville, FL, United States of America aff001;  McKnight Brain Institute, University of Florida, Gainesville, FL, United States of America aff002;  Department of Biomedical Engineering, University of Florida, Gainesville, FL, United States of America aff003;  Department of Civil and Coastal Engineering, University of Florida, Gainesville, FL, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222957

Souhrn

The ventral midbrain supports a variety of functions through the heterogeneity of neurons. Dopaminergic and GABA neurons within this region are particularly susceptible targets of amphetamine-class psychostimulants such as methamphetamine. While this has been evidenced through single-neuron methods, it remains unclear whether and to what extent the local neuronal network is affected and if so, by which mechanisms. Both GABAergic and dopaminergic neurons were heavily featured within the primary ventral midbrain network model system. Using spontaneous calcium activity, our data suggest methamphetamine decreased total network output via a D2 receptor-dependent manner. Over culture duration, functional connectivity between neurons decreased significantly but was unaffected by methamphetamine. However, across culture duration, exposure to methamphetamine significantly altered changes in network assortativity. Here we have established primary ventral midbrain networks culture as a viable model system that reveals specific changes in network activity, connectivity, and topology modulation by methamphetamine. This network culture system enables control over the type and number of neurons that comprise a network and facilitates detection of emergent properties that arise from the specific organization. Thus, the multidimensional properties of methamphetamine can be unraveled, leading to a better understanding of its impact on the local network structure and function.

Klíčová slova:

Biology and life sciences – Cell biology – Cellular types – Animal cells – Signal transduction – Cell signaling – Calcium signaling – Neuroscience – Cellular neuroscience – Neurons – Neural networks – Computational neuroscience – Single neuron function – Dopaminergics – Gamma-aminobutyric acid – Anatomy – Brain – Brainstem – Midbrain – Computational biology – Biochemistry – Neurochemistry – Neurochemicals – Neurotransmitters – Biogenic amines – Catecholamines – Dopamine – Hormones – Computer and information sciences – Medicine and health sciences – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Amines – Organic chemistry


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