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-HT receptors prevented the inhibitory component of MDMA action and the emergence of the gradient, indicating that activation of 5-HT 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.

Septotemporal variation in beta-adrenergic modulation of short-term dynamics in the hippocampus

“…Short-term dynamics of neuronal activity profoundly regulate neural information flow in local circuits ( Abbott and Regehr, 2004 , Jackman and Regehr, 2017 , Pariz et al, 2018 ) and neuromodulation represents a basic mechanism that determines or shapes information transfer between neural elements ( Ito and Schuman, 2008 ). Importantly, neuromodulatory actions of several neuromodulators may considerably differ along the septotemporal axis of the hippocampus, see examples in Malik and Johnston, 2017 , Dubovyk and Manahan-Vaughan, 2018 , Mlinar and Corradetti, 2018 , Papaleonidopoulos et al, 2018 ), and have significant implications in hippocampal physiology and pathology, discussed in Gulyaeva (2019 ). Neuromodulation is one aspect of the diversification in functional organization along the longitudinal axis of the hippocampus.…”

Septotemporal variation in modulation of synaptic transmission, paired-pulse ratio and frequency facilitation/depression by adenosine and GABAB receptors in the rat hippocampus

“…Recent evidence shows that neuromodulation play significant roles in diversifying the functions of the local neuronal network along the hippocampus ( Dubovyk and Manahan-Vaughan, 2018 ; Grigoryan and Segal, 2013 ; Maggio and Segal, 2007 ; Malik and Johnston, 2017 ; Mlinar and Corradetti, 2018 ; Papaleonidopoulos et al, 2018 ; Reis et al, 2019 ). Interestingly, working memory which may engage changes in short-term synaptic plasticity ( Devaraju et al, 2017 ; Le Barillier et al, 2015 ; Pals et al, 2020 ) and is amenable to neuromodulation ( Cardoso-Cruz et al, 2014 ; McHugh et al, 2008 ) may involve a distinct participation of the dorsal (posterior) and ventral (anterior) hippocampus, as recent evidence suggests ( Hauser et al, 2020 ; Li et al, 2022 ).…”

Serotonin Deficiency Increases Context-Dependent Fear Learning Through Modulation of Hippocampal Activity

“…Although the protocol applied for the LTP and the behavioral experiments differed and, therefore, quantitative correlation of plasticity impairment with the behavioral effects was not possible, our results demonstrate that 5-HT is required for foot shock-induced impairment of LTP. Indeed, 5-HT has been shown to shift hippocampal activity along the longitudinal axis toward the ventral part (Mlinar and Corradetti, 2018). Thus, an absence of this mechanism in Tph2 -/- mice may result in an overactivation of the hippocampal circuitry, manifested as enhanced c-Fos immunostaining and overrepresentation of the contextual component in fear learning.…”

“…In this respect, it may be of interest in a follow up study to analyze the response of the ventral hippocampus, which is involved in emotional fear processing (Fanselow and Dong, 2010), and is modulated differentially by 5-HT along its longitudinal axis (Mlinar and Corradetti, 2018).…”