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      Plasticity in Preganglionic and Postganglionic Neurons of the Sympathetic Nervous System during Embryonic Development

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          Abstract

          Sympathetic preganglionic neurons (SPNs) are the final output neurons from the central arm of the autonomic nervous system. Therefore, SPNs represent a crucial component of the sympathetic nervous system for integrating several inputs before driving the postganglionic neurons (PGNs) in the periphery to control end organ function. The mechanisms which establish and regulate baseline sympathetic tone and overall excitability of SPNs and PGNs are poorly understood. The SPNs are also known as the autonomic motoneurons (MNs) as they arise from the same progenitor line as somatic MNs that innervate skeletal muscles. Previously our group has identified a rich repertoire of homeostatic plasticity (HP) mechanisms in somatic MNs of the embryonic chick following in vivo synaptic blockade. Here, using the same model system, we examined whether SPNs exhibit similar homeostatic capabilities to that of somatic MNs. Indeed, we found that after 2-d reduction of excitatory synaptic input, SPNs showed a significant increase in intracellular chloride levels, the mechanism underlying GABAergic synaptic scaling in this system. This form of HP could therefore play a role in the early establishment of a setpoint of excitability in this part of the sympathetic nervous system. Next, we asked whether homeostatic mechanisms are expressed in the synaptic targets of SPNs, the PGNs. In this case we blocked synaptic input to PGNs in vivo (48-h treatment), or acutely ex vivo, however neither treatment induced homeostatic adjustments in PGN excitability. We discuss differences in the homeostatic capacity between the central and peripheral component of the sympathetic nervous system.

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          A series of normal stages in the development of the chick embryo

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            Activity-dependent scaling of quantal amplitude in neocortical neurons.

            Information is stored in neural circuits through long-lasting changes in synaptic strengths. Most studies of information storage have focused on mechanisms such as long-term potentiation and depression (LTP and LTD), in which synaptic strengths change in a synapse-specific manner. In contrast, little attention has been paid to mechanisms that regulate the total synaptic strength of a neuron. Here we describe a new form of synaptic plasticity that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity. Chronic blockade of cortical culture activity increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) without changing their kinetics. Conversely, blocking GABA (gamma-aminobutyric acid)-mediated inhibition initially raised firing rates, but over a 48-hour period mESPC amplitudes decreased and firing rates returned to close to control values. These changes were at least partly due to postsynaptic alterations in the response to glutamate, and apparently affected each synapse in proportion to its initial strength. Such 'synaptic scaling' may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs, as well as stabilizing synaptic strengths during Hebbian modification and facilitating competition between synapses.
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              Excitatory actions of gaba during development: the nature of the nurture.

              In the immature brain, GABA (gamma-aminobutyric acid) is excitatory, and GABA-releasing synapses are formed before glutamatergic contacts in a wide range of species and structures. GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions. I propose that this mechanism provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation while avoiding the potentially toxic effects of a mismatch between GABA-mediated inhibition and glutamatergic excitation. As key elements of this cascade are activity dependent, the formation of inhibition adds an element of nurture to the construction of cortical networks.
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                Author and article information

                Journal
                eNeuro
                eNeuro
                eneuro
                eNeuro
                eNeuro
                Society for Neuroscience
                2373-2822
                13 October 2023
                3 November 2023
                November 2023
                : 10
                : 11
                : ENEURO.0297-23.2023
                Affiliations
                [1]Department of Cell Biology, Emory University School of Medicine , Atlanta, GA 30322
                Author notes

                The authors declare no competing financial interests.

                Author contributions: A.R. and P.W. designed research; A.R., D.P., and P.W. performed research; A.R. and P.W. analyzed data; A.R., D.P., and P.W. wrote the paper.

                This work was supported by National Institute of Neurological Disorders and Stroke Grants R01NS065992, R21NS106325, and F31NS118867.

                Correspondence should be addressed to Peter Wenner at pwenner@ 123456emory.edu .
                Author information
                https://orcid.org/0000-0002-7072-2194
                Article
                eN-NWR-0297-23
                10.1523/ENEURO.0297-23.2023
                10630925
                37833062
                e7f65701-64d5-439d-b561-7db1fb399752
                Copyright © 2023 Ratliff et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 15 August 2023
                : 30 September 2023
                : 4 October 2023
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 68, Pages: 13, Words: 00
                Funding
                Funded by: HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS), doi 10.13039/100000065;
                Award ID: R01NS065992
                Award ID: R21NS106325
                Award ID: 1F31NS118867
                Categories
                2
                Research Article: New Research
                Development
                Custom metadata
                November 2023

                autonomic nervous system,chick embryo,homeostatic plasticity,sympathetic nervous system,synaptic scaling

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