| Abstract |
Anxiety is an aversive emotional state reflecting the expectation of potential threats. The
ventral hippocampus (vHip) is a key brain region for the genesis of anxiety responses. Recent
studies have shown that anxiety is mediated by the recruitment of pyramidal neurons from
the vHip (anxiety neurons) targeting various limbic structures. Despite the function of the
vHip in triggering emotional responses, whether the vHip also signals the anticipation of an
anxiogenic experience remains elusive. To address this question, we developed a novel trial-
based rodent anxiety behavioural task called the forced emotional-shifting task (FEST), with
separate temporal and spatial contexts for the anxiogenic experience and its anticipation. By
performing in vivo single-unit recordings from the vHip of freely moving mice, we identified
both anxiety neurons as well as a distinct neuronal population with ramping activity in the
safe compartment of the forced emotional-shifting task, suggestive of an anticipatory coding
for anxiety. The activity of these anticipatory neurons intrinsically depended on the
experience of anxiety, indicating that anticipatory neurons are not the mere result of novelty
or time processing. Moreover, unpredictable time intervals impaired the formation of
anticipatory neurons, while long structured time intervals enhanced their response. The
activity of anxiety neurons correlated with the magnitude of the anticipatory signal.
Optogenetic silencing of the vHip activity in the safe compartment led to lower anxiety-
related neuronal activity, indicating a possible functional interaction between anticipatory
and anxiety neurons. Collectively, our results suggest that anxiety processing comprises
different stages, with distinct neuronal populations within the vHip mediating anxiety or its
anticipation. |
