ePoster

Soma-targeted GECI constructs for intracerebral or intravenous administration, including jGCaMP8, NEMO, and eGCaMP constructs

Sverre Grødem, Ingeborg Nymoen, Guro H. Vatne, Fredrik S. Rogge, Valgerdur Björnsdottir, David G. Hildebrand, Andre Berndt, Kristian Lensjø, Marianne Fyhn
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Sverre Grødem, Ingeborg Nymoen, Guro H. Vatne, Fredrik S. Rogge, Valgerdur Björnsdottir, David G. Hildebrand, Andre Berndt, Kristian Lensjø, Marianne Fyhn

Abstract

Genetically encoded Ca2+ indicators (GECIs) are widely used to measure neural activity. Here, we explore the use of systemically administered PHP.eB AAVs for brain-wide expression of GECIs and compare the expression properties to intracerebrally injected AAVs in male mice. We show that systemic administration is a promising strategy for imaging neural activity. Next, we establish the use of EE-RR- (soma) and RPL10a (Ribo) soma-targeting peptides with the latest jGCaMP and show that EE-RR-tagged jGCaMP8 gives rise to strong expression but limited soma-targeting. In contrast, Ribo-tagged jGCaMP8 lacks neuropil signal, but the expression rate is reduced. To combat this, we modified the linker region of the Ribo-tag (RiboL1-). RiboL1-jGCaMP8 expresses faster than Ribo-jGCaMP8 but remains too dim for reliable use with systemic virus administration. However, intracerebral injections of the RiboL1-tagged jGCaMP8 constructs provide strong Ca2+ signals devoid of neuropil contamination, with remarkable labeling density. We also benchmark the recently developed, mNeonGreen based GECI NEMO, as well as eGCaMP2+. We compare the performance of these new GECIs to jGCaMP8 in-vivo, and introduce the first soma-targeted versions of these sensors.

Unique ID: fens-24/soma-targeted-geci-constructs-intracerebral-f05d45a2