Differential modulation of CA1 impulse flow by endogenous serotonin along the hippocampal longitudinal axis

Abstract The hippocampus is functionally differentiated along its longitudinal axis, with the dorsal and ventral segments preferentially involved in cognitive and emotional processing, respectively. Serotonergic modulation of hippocampal function has been extensively studied, but its relation to the dorsoventral axis has remained largely unknown. To examine the modulation of hippocampal output along the dorsoventral axis by endogenous serotonin (5-HT) we compared the effect of the 5-HT/noradrenaline (NA)-releaser, 3,4-methylenedioxymethamphetamine (MDMA), in transversal slices encompassing the entire rat hippocampus. Co-release of 5-HT and NA by MDMA resulted in a gradient of effects on evoked population spikes in the CA1 area along the dorsoventral axis of the hippocampus. Selective 5-HT release decreased population spike amplitude in slices from dorsal hippocampus, whereas an increase was produced in the ventral hippocampus, indicating differential modulation of CA1 impulse flow along the dorsoventral axis by endogenous 5-HT. Selective NA release increased population spike amplitude with no gradient indicating facilitatory effect of endogenous NA along the entire dorsoventral axis. Blockade of 5-HT1A receptors prevented the inhibitory component of MDMA action and the emergence of the gradient, indicating that activation of 5-HT1A receptors is required for differential modulation of CA1 impulse flow by endogenous 5-HT. These findings suggest that a dorsoventral shift in CA1 output level may represent an integral component of 5-HT action on hippocampal information processing. Given the preferential role of ventral hippocampus in emotional and anxiety-related behavior, it can be proposed that serotonin tone encodes the emotional salience of the signal processed by hippocampus.