ATP released from astrocytes modulates action potential threshold and spontaneous excitatory postsynaptic currents in the neonatal rat prefrontal cortex. 2017

Edward Beamer, and Gergely Kovács, and Beata Sperlágh
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.

Maternal immune activation during pregnancy is a risk factor for neurodevelopmental disorders, such as schizophrenia; however, a full mechanistic understanding has yet to be established. The activity of a transient cell population, the subplate neurons, is critical for the development of cortical inhibition and functional thalamocortical connections. Sensitivity of these cells to factors released during inflammation, therefore, may offer a link between maternal immune activation and the aberrant cortical development underlying some neuropsychiatric disorders. An elevated extracellular ATP concentration is associated with inflammation and has been shown to have an effect on neuronal activity. Here, we investigated the effect of ATP on the electrophysiological properties of subplate neurons. Exogenous ATP increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) at micromolar concentrations. Further, ATP released by astrocytes activated by the PAR-1 agonist, TFLLR-NH2, also increased the amplitude and frequency of sEPSCs in subplate neurons. The electrophysiological properties of subplate neurons recorded from prefrontal cortical (PFC) slices from neonatal rats were also disrupted in a maternal immune activation rat model of schizophrenia, with a suramin-sensitive increase in frequency and amplitude of sEPSCs. An alternative neurodevelopmental rat model of schizophrenia, MAM-E17, which did not rely on maternal immune activation, however, showed no change in subplate neuron activity. Both models were validated with behavioral assays, showing schizophrenia-like endophenotypes in young adulthood. The purinergic modulation of subplate neuron activity offers a potential explanatory link between maternal immune activation and disruptions in cortical development that lead to the emergence of neuropsychiatric disorders.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005260 Female Females
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D001253 Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury. Astroglia,Astroglia Cells,Astroglial Cells,Astrocyte,Astroglia Cell,Astroglial Cell,Astroglias,Cell, Astroglia,Cell, Astroglial
D013498 Suramin A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Germanin,Moranil,Naganin,Naganol,Naphuride,Suramin Sodium,Suramin, Hexasodium Salt,Suramin, Monosodium Salt,Hexasodium Salt Suramin,Monosodium Salt Suramin,Salt Suramin, Hexasodium,Salt Suramin, Monosodium,Sodium, Suramin

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