NMDARs hypofunction in parvalbumin-expressing interneurons alters oscillations and sensory tuning in mouse primary visual cortex

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URI: http://hdl.handle.net/10900/84727
Dokumentart: Dissertation
Date: 2020-10-15
Language: English
Faculty: 4 Medizinische Fakultät
Department: Graduiertenkollegs
Advisor: Busse, Laura (Prof. Dr.)
Day of Oral Examination: 2018-08-01
DDC Classifikation: 500 - Natural sciences and mathematics
610 - Medicine and health
Keywords: Neuropsychologie
Other Keywords: Kognitive Neurowissenschaft
mouse visual cortex
License: Publishing license excluding print on demand
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Sensory information transmission crucially depends on a correct interplay between synaptic excitation and synaptic inhibition. In this dynamic balance observed in neural circuits, inhibition is thought to be critical to achieve network stability and gate information processing; however, how inhibition itself contributes to the selectivity and sensitivity of neuronal responses to sensory stimuli is still, currently, a matter of intense debate. Furthermore, there is little evidence about the cellular mechanisms that might underlie such shaping of responses by inhibitory interneurons in vivo. In primary visual cortex (V1), for instance, parvalbumin-positive (PV+) inhibitory interneurons control network oscillations, set the gain of sensory responses, and contribute to spatial integration. Interestingly, these aspects of visual processing are often disturbed in several neuropsychiatric disorders, amongst them schizophrenia, where one hypothesis proposes that hypofunctioning NMDA-glutamate receptors (NMDAR) might cause deficient excitatory drive to PV+ interneurons. However, little is known on how genetic modifications specifically causing NMDAR hypofunction in PV+ interneurons, can affect neural responses to visual stimuli. To test how NMDAR hypofunction in PV+ interneurons affects V1 network and visual tuning properties, I compared extracellular activity between control and transgenic mice lacking NMDAR-mediated glutamatergic excitation of PV+ neurons. I found frequency-specific alterations of visual cortex oscillatory power, and enhanced contrast sensitivity and stronger surround suppression in V1 putative pyramidal cells. Importantly, network oscillations and contrast processing were unaltered in the dorsolateral geniculate nucleus (dLGN) of the thalamus, indicating that the observed disruptions of V1 activity are mediated by changes in cortical networks. I conclude that reduced glutamatergic excitation of cortical PV+ interneurons plays a critical role in visual information processing, as it is sufficient to alter V1 rhythms and tuning properties; this is also consistent with the structural and functional alterations previously observed in visual cortex of schizophrenia patients, and further supports the involvement of PV+ interneurons hypofunctionality in the disease etiology.

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