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GABAergic interneurons control spiking of adult-born hippocampal granule cells via nonlinear α5-GABAA receptors

Lodge, Meredith. GABAergic interneurons control spiking of adult-born hippocampal granule cells via nonlinear α5-GABAA receptors. 2019, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_13508

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Abstract

Excitatory GABAergic synapses have been shown to promote development and maturation of newborn granule cells in the adult hippocampus. In addition, strong GABAergic synaptic inputs are known to generate effective shunting inhibition in these young neurons. However, the functional properties of the GABA receptors mediating excitation and inhibition are largely unknown. Here we analyzed GABA receptors in young neurons activated by soma-targeting parvalbumin and dendrite-targeting somatostatin inhibitory interneurons. The synaptic GABAA receptors in young neurons show a pronounced non-linear voltage dependence and are assembled in part by a5- subunits. As a consequence, synaptic conductance is 4-fold larger around the AP threshold (-35 mV) as compared to the resting potential (-80mV), independent of the interneuron subtype. By contrast, in mature granule cells, parvalbumin interneurons mediate linear GABAergic synaptic currents lacking a5-subunits. Blocking a5-GABAA- receptor-mediated synaptic currents in young neurons not only reduced GABAergic depolarization, but also effectively reduced shunting inhibition of AP generation. Taken together, this data shows that nonlinear GABAA receptors support both GABAergic depolarization and effective GABAergic shunting inhibition in newborn young granule cells of the adult hippocampus.
Advisors:Bischofberger, Josef and Rinaldi Barkat, Tania
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Cellular Neurophysiology (Bischofberger)
05 Faculty of Science
UniBasel Contributors:Lodge, Meredith and Bischofberger, Josef
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13508
Thesis status:Complete
Number of Pages:1 Online-Ressource (97 Seiten)
Language:English
Identification Number:
Last Modified:18 Feb 2020 05:30
Deposited On:17 Feb 2020 14:01

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