Activity-dependent regulation of the gabaergic synapse
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2021
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Universidad de Valparaíso
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Programa de Magister en Ciencias Biologicas Mencion Neurocienciass
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ABSTRACT:
Excitatory and inhibitory balance play a fundamental role in regulation and maintenance of cerebral activity. Inhibitory regulation occurs by the action of diverse GABAergic cells that show activity-dependent changes. Here, we focus on plasticity of inhibitory synapses mediated by somatostatin-expressing interneurons (SOM-INs) and parvalbumin-expressing interneurons (PV-INs). On pyramidal cells, SOM-INs make distal dendritic synapses, while PV-INs make perisomatic synapses. We first discuss the properties of these interneurons and the circuits in which they are embedded to set the theoretical background of this thesis work. Then, we reviewed the diverse forms of inhibitory synaptic plasticity in the literature that mostly disregards the contribution of specific interneuron types. Lastly, through various means of triggering synaptic activity in brain slices, including NMDA application, electrical stimulation and optogenetic activation, in this study, we aim to experimentally compare and contrast the inducibility of plasticity of these two major types of GABAergic synapses on pyramidal cells. In our hands, NMDA activation potentiates inhibition mediated by SOMINs (138.48% increase), while leaving PV-IN synapses unchanged, suggesting that NMDAR activation preferentially modifies distinct types of inhibitory synapses. Our evidence suggests that this plasticity involves postsynaptic changes. While on average, neither electrical nor optogenetic afferent stimulation induced plasticity in both synapses studied, further analysis of individual experiments suggest multiple forms of plasticity were induced. Of note, PV-IN synapses showed a greater predisposition to plasticity than those formed by SOM-INs (90.9% vs 60%). In both synapse types, long-term depression was most frequently observed but with apparently different expression mechanisms. Thus, through discussion of existing literature and experimental studies, we propose that GABAergic synapses are molecularly diverse and follow specific plasticity rules that is linked to the identity of the presynaptic interneuron.
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ACTIVIDAD NERVIOSA SUPERIOR, PLASTICIDAD NEURONAL