18F-fallypride-binding potential was consistent with previous studies, exhibiting strongest uptake in regions such as the striatum where D2 D3 are highly expressed, and whole brain standardised uptake value (SUV) variation was within the typical
15 min free exploration period (Fig. 1A) ll mice spent at least 25% of the time actively engaged in a
specific behaviour other than sitting (“Im”
or “immobility” ) or transitioning between behaviours (
“ null”). nassisted rearing, ranging from 0.3% to 21.0% (CV = 0.79), exhibited the most variation of the
behaviours performed by all animals (Fig. 1B). he behaviour with the least variation was object
interaction (CV = 0.12). All subjects spent more time walking near the walls of the arena than in the centre, as
expected, and overall behavioural performance was consistent with investigations
e next used a correlation matrix to perform unbiased comparisons
between the two datasets both expected and unexpected outcomes (Fig. 1E).
First, unassisted rearing (canonical exploratory behaviour performed by
micedemonstrated an inverse correlation with 18F-fallypride SUV throughout the brain, suggesting either a
brain-wide internalisation of D3 or an increase in dopamine release throughout most of the brain.
We favour the latter interpretation since novel environments the one employed in this study are known to
increase the firing rate of dopamine neuronsWhat our study adds to this knowledge is
the degree of VTA activation corresponds to the degree of exploration within novel
environment, even when the degree of absolute novelty remains constant. f demonstrating a negative correlation between 18F-fallypride SUV and
unassisted rearing, the hippocampus and amygdala showed the strongest Pearson’s r. opamine
projections to these specific regions may be the most strongly activated by sensorium-enriching exploratory
The association between dopaminergic signalling and the hippocampus strong correlation with the amygdala surpris . VTA-amygdalar dopamine is proposed to signal danger and increased dopamine release occurs in response
to stressmore unassisted rearing in the safe novel environment would not be
expected to indicate more stress. 18F-fallypride amygdala during word pair association tasks
Second, we observed that SUVs within the superior and inferior colliculi did not correlate strongly with any of the
scored behaviours, suggesting D2/D3 receptors in the colliculi do not play a major role in the18F-fallypride uptake in the
colliculi a functional separation of dopamine neurons that project to the colliculi compared to
other target regions. Both of these ideas are consistent with the seemingly specific role for dopamine signalling in
the colliculi behavioural responses to aversive or fearful stimuliOur experiment
examined well-handled subjects in a non-fearful environment. In this context, D2/D3 receptor expression level
and/or dopamine release in the colliculi would not be expected to play any major role.
under the conditions used in this study. he special lack of correlations for
Third, the strongest correlations between behaviour and 18F-fallypride SUV emerged when examining head
grooming (grooming anywhere in the face and head region while standing upright on hind legs). In behavioural
literature, head grooming is rarely on its own, even when grooming microstructure is being examined as
a proxy for internal states like anxietygrooming initiation is known to be governed by dopaminergic signalling, and he strong correlations scents heir paws .
Finally, we assessed the feasibility of merging small animal PET and behavioural analyses using a Pearson’s r
power analysis. Without considering multiple comparisons, sample sizes of 10 to 15 animals would be needed
to obtain statistical significance for stronger correlations (e.g. hippocampus 18F-fallypride and unassisted
rearing). When considering multiple comparisons, highly
dependent on strength. For weaker correlations in the 0.6 range, multiple comparisons inflate
the required sample size up to 25 30 subjects. Stronger correlations Pearson’s r are hardly affected by multiple comparisons, indicating sample sizes in the 1015 range ould still be .