fMRI Fingerprint of Memory and Spatial Navigation System

This application covers our laboratory's use of the anatomical specificity engendered by genetically modified mice to explore and map the global fMRI fingerprints of the functional circuitry of memory and spatial navigation. Towards this end we use novel genetically modified rodents (designed by our collaborators) to specifically address whole-brain circuit-level questions. These animals express genes in specific populations of neurons that allow us to determine the anatomical and functional connectivity of the elements of native neural circuits. Using functional resonance imaging (fMRI) we will investigate the activity patterns in the entire rodent brain resulting from activation of these specific neuronal populations. We then compare and contrast the activity resulting from varying the activity levels of the different neuronal populations, in order to understand (on a brain-wide level) the active areas and global activation patterns involved in spatial navigation and memory. These resulting 'global fingerprints' will be used in translational work to inform human MRI studies of memory and spatial navigation which is ongoing in our laboratory, and where such manipulations of the circuit is not possible. In order to enable direct comparison to human studies using the same techniques, it will be critical to carry out a portion of the experiments in awake animals, as anesthesia has been reported to temporarily alter functional brain connectivity and activity levels while under sedation. As some of the experiments will be carried out in awake, head-restrained animals while they are subjected to the sounds from the scanner, this is likely to cause some distress or the animals, which we will mitigate by protecting their ear canals (as is done in humans), and careful and gradual habituation to the physical restraints and sounds.

To get an MRI fingerprint for each cell population we will use nine different rodent lines, and carry out anesthetized, awake and optogenetic manipulations in each of the lines. We estimate that in total for the four years we will need 958 animals (868 mice, 90 rats). As the necessary genetic expression from breeding of the lines is never 100%, we will use the non-positive siblings as control animals, eliminating the need for additional animals for the study. This will also improve the quality of the study by reducing the variability between the animals in the experimental group and the control group. In order to make improvements rapidly, and reduce the number of necessary animals we will base our work on pilot studies that have been carried out in a collaborating lab in Lisboa, Portugal. As we progress, we will aim to continuously optimize our techniques.

Den kumulative belastningen av planlagte prosedyrer og langvarig oppstalling alene kan bli betydelig.

Forsøket har ikke vært gjennomført slik som opprinnelig planlagt.
Forskergruppen og forsøksansvarlig er siden 2019 ikke lenger tilknyttet forsøksdyravdelingen ved NTNU.
Den kumulative belastningen av planlagte prosedyrer, som omfattet kranial kirurgi, MRI-scanning av våkne dyr og langvarig oppstalling av forsøkdyr alene, ble vurdert som betydelig da forsøket ble godkjent i 2017.

Forsøket ble godkjent for bruk av 868 mus og 90 rotter.

Belastningsgraden ble vurdert som betydelig for dyr som skulle gjennomgå kranial kirurgi, MRI-scanning i våken tilstand og langvarig oppstalling alene. Disse prosedyrene er bare delvis gjennomført, og det er derfor ikke samsvar mellom antatt og faktisk belastningsgrad.

Dyrene ble scannet med MRI under anestesi, noen av musene hadde gjennomgått kirurgi. MRI-scanning av våkne dyr ble ikke gjennomført.

Forsøket ble avbrutt før fullføring, og det er brukt til sammen 8 mus og 33 rotter i forsøk.

Det er derfor ikke grunnlag for å vurdere om forsøksdesign, antall dyr, prosedyrer og scoringsskjema/humane endepunkter kunne vært forbedret.