Optogenetic silencing of Parvalbumin-expressing hippocampal interneurons

Medientyp: E-Book

Titel: Optogenetic silencing of Parvalbumin-expressing hippocampal interneurons

Beteiligte: Strüber, Michael [Verfasser:in]; Bartos, Marlene [Akademische:r Betreuer:in]; Bartos, Marlene [Sonstige Person, Familie und Körperschaft]; Diester, Ilka [Sonstige Person, Familie und Körperschaft]

Körperschaft: Albert-Ludwigs-Universität Freiburg, Medizinische Fakultät

Erschienen: Freiburg: Universität, 2022

Umfang: Online-Ressource

Sprache: Englisch

DOI: 10.6094/UNIFR/228310

Identifikator:

Schlagwörter: Interneurons ; Neurobiologie ; Synapse ; (local)doctoralThesis

Entstehung:

Hochschulschrift: Dissertation, Universität Freiburg, 2022

Anmerkungen:

Beschreibung: Abstract: Neuronal information is encoded and transmitted in the action potential pattern of neurons. Which cells are active at which time point depends not only on their excitatory but also on their inhibitory synaptic inputs. Inhibition is supplied by a complex network of inhibitory, predominantly Gamma-amino-hydroxy-butyric acid releasing (GABAergic) interneurons. The large scale interaction between excitatory and inhibitory cells in brain networks brings about stereotypical electrical oscillations in different frequency ranges, which are hypothesized to play an important role for neuronal information processing. Among the many types of GABAergic interneurons, perisoma-inhibiting Parvalbumin-expressing interneurons (PVIs) are thought to stand at the center of action potential control in postsynaptic target cells and to be essential components of oscillating neuronal networks.<br>In this work, I set out to directly investigate the effects of PVIs on spiking activity and oscillations in the murine hippocampus, a well-described brain area involved in spatial orientation, memory formation and emotional processing. To dynamically control the activity of PVIs without long-term adaptation mechanisms, I made use of the photoactive inhibitory chloride pump eNpHR (Halorhodopsin), which effectively silences the expressing cells upon light stimulation at the correct wavelength (e.g. 561 nm). I recorded neurons in different dorsoventral depths corresponding to different hippocampal subregions. <br>Upon exposure to light at 561 nm, most recorded neurons did not significantly change their average firing frequency. Only a fraction of ~16% showed light responsive firing rate modulation. 5% of all recorded neurons responded to light stimulation by a reduction in firing rate, in part due to direct optogenetic silencing. The remaining 11%, comprising excitatory pyramidal cells but also inhibitory interneurons, increased their activity. Oscillatory activity in the recorded brain regions was not affected at all by PVI inhibition. However, in general, CA1 interneurons and principal cells seemed to be less likely to couple to local gamma and theta oscillation phases. <br>Thus, optogenetic silencing of hippocampal PVIs seems to have a mild net excitatory effect on the activity level of hippocampal neurons. Furthermore, it interferes with phase coupling of principal and interneuron spikes to specific network oscillations while leaving the oscillatory structure itself unaffected

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