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Role of the AMPA receptor auxiliary subunit CKAMP44 in the olfactory bulb

Kegel, Marcel

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Abstract

The olfactory bulb is the first processing station of olfactory information. Mitral and tufted cells, which are the output neurons of the olfactory bulb, receive input from olfactory sensory neurons. The activity of the output neurons is controlled by inhibitory periglomerular and granule cells. Periglomerular cells also receive excitatory input from olfactory sensory neurons and provide feedforward inhibition. Little is known about how AMPA receptor number and function in synapses of periglomerular cells is controlled. It is also not well understood how changes in AMPA receptor number of periglomerular cells affect the olfactory bulb network. Here I show with fluorescence in situ hybridization that the AMPA receptor auxiliary protein CKAMP44 is expressed at high levels in periglomerular cells, but not or only at low levels in other neurons of the olfactory bulb. With ex vivo slice electrophysiology I found that deletion of CKAMP44 decreases AMPA receptor-mediated currents in periglomerular cells. This in turn reduces the inhibition from periglomerular cells onto mitral cells and increases mitral cell activity upon olfactory sensory neuron activation. Data from a computational model of olfactory bulb neuron activity corroborate these findings and indicate that feedforward inhibition from periglomerular cells reduces mitral cell activity in particular during weak or intermediate excitation from olfactory sensory neurons. Behavior experiments showed that the function of the olfactory bulb, at least concerning the differentiation of odors, is not affected by decreased periglomerular cell excitability. Whether other odor functions (e.g. detection threshold) and in vivo network activity is affected remains to be investigated.

Item Type: Dissertation
Supervisor: Monyer, Prof. Dr. Hannah
Place of Publication: Heidelberg
Date of thesis defense: 15 June 2020
Date Deposited: 30 Sep 2020 06:47
Date: 2020
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
Subjects: 570 Life sciences
Controlled Keywords: Neurobiologie, Glutamate
Uncontrolled Keywords: AMPA receptor auxiliary subunit, CKAMP44
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