Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation

Teixeira, Cátia M.; Rosen, Zev B.; Suri, Deepika; Sun, Qian; Hersh, Marc; Sargin, Derya; Dincheva, Iva; Morgan, Ashlea A.; Spivack, Stephen; Krok, Anne C.; Hirschfeld-Stoler, Tessa; Lambe, Evelyn K.; Siegelbaum, Steven A.; Ansorge, Mark S.

doi:10.1016/j.neuron.2018.04.030

Cited by 95 publications

(88 citation statements)

References 61 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of optogenetic techniques to selectively stimulate neuromodulator release has highlighted differences between exogenous bath-applied and endogenous release of dopamine and serotonin in ex vivo brain slice experiments ( Rosen et al. 2015 ; Teixeira et al. 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors

2020

View full text Add to dashboard Cite

Abstract Release of the neuromodulator noradrenaline signals salience during wakefulness, flagging novel or important experiences to reconfigure information processing and memory representations in the hippocampus. Noradrenaline is therefore expected to enhance hippocampal responses to synaptic input; however, noradrenergic agonists have been found to have mixed and sometimes contradictory effects on Schaffer collateral synapses and the resulting CA1 output. Here, we examine the effects of endogenous, optogenetically driven noradrenaline release on synaptic transmission and spike output in mouse hippocampal CA1 pyramidal neurons. We show that endogenous noradrenaline release enhances the probability of CA1 pyramidal neuron spiking without altering feedforward excitatory or inhibitory synaptic inputs in the Schaffer collateral pathway. β-adrenoceptors mediate this enhancement of excitation-spike coupling by reducing the charge required to initiate action potentials, consistent with noradrenergic modulation of voltage-gated potassium channels. Furthermore, we find the likely effective concentration of endogenously released noradrenaline is sub-micromolar. Surprisingly, although comparable concentrations of exogenous noradrenaline cause robust depression of slow afterhyperpolarization currents, endogenous release of noradrenaline does not, indicating that endogenous noradrenaline release is targeted to specific cellular locations. These findings provide a mechanism by which targeted endogenous release of noradrenaline can enhance information transfer in the hippocampus in response to salient events.

show abstract

Section: Discussionmentioning

confidence: 99%

Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors

2020

View full text Add to dashboard Cite

show abstract

“…Serotonin (5-HT) receptors are composed of seven families (5-HT 1 to 5-HT 7 ) which are coupled to GPCRs except for the ionotropic 5-HT 3 receptors and all 5-HT receptors are expressed in the hippocampus. Serotonin has been shown to increase cellular excitability by several mechanisms ( Figure 2 ), such as inhibition of K + channels [ 62 ], and serotonin also enhances NMDAR activation [ 63 ] and facilitates LTP expression in CA1 [ 64 , 65 •• , 66 ]. Stimulation of interneurons and astrocytes by activation of 5-HT receptors has been reported [ 67 , 68 ] but it is not yet clear whether this can also facilitate LTP.…”

Section: Serotoninmentioning

confidence: 99%

Neuromodulation of hippocampal long-term synaptic plasticity

Palacios-Filardo

Mellor

2019

Current Opinion in Neurobiology

127

105

View full text Add to dashboard Cite

Multiple neuromodulators including acetylcholine, noradrenaline, dopamine and serotonin are released in response to uncertainty to focus attention on events where the predicted outcome does not match observed reality. In these situations, internal representations need to be updated, a process that requires long-term synaptic plasticity. Through a variety of common and divergent mechanisms, it is recently shown that all these neuromodulators facilitate the induction and/or expression of long-term synaptic plasticity within the hippocampus. Under physiological conditions, this may be critical for suprathreshold induction of plasticity endowing neuromodulators with a gating function and providing a mechanism by which neuromodulators enable the targeted updating of memory with relevant information to improve the accuracy of future predictions.

show abstract

“…We also evaluated exploratory and anxiety-like behaviors in the OFT (Seibenhener and Wooten, 2015;Teixeira et al, 2018). Mice were placed in the periphery of a brightly illuminated open field (42 cm x 42 cm x 30 cm) and allowed to explore the arena for 10 minutes and then returned to their home cage.…”

Section: Oftmentioning

confidence: 99%

Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice

Botterill

Vinod

Gerencer

et al. 2020

Preprint

View full text Add to dashboard Cite

ABSTRACTThe dentate gyrus (DG) of the hippocampus is important for cognitive and affective behaviors. However, the circuits underlying these behaviors are unclear. DG mossy cells (MCs) have been a focus of attention because of their excitatory synapses on the primary DG cell type, granule cells (GCs). However, MCs also activate DG GABAergic neurons which inhibit GCs. We took advantage of specific methods and a gain- and loss-of function strategy with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to study MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some but not all types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate early gene c-Fos to address whether DREADDs bidirectionally regulated MC or GC activity. We confirmed excitatory DREADDs increased MC c-Fos. However, there was no change in GC c-Fos, consistent with MC activation leading to GABAergic inhibition of GCs. In contrast, inhibitory DREADDs led to a large increase in GC c-Fos, consistent with a reduction in MC excitation of GABAergic neurons, and reduced inhibition of GCs. Taken together, these results suggest that MCs regulate anxiety and cognition in specific ways. We also raise the possibility that cognitive performance may be improved by reducing anxiety.SIGNIFICANCE STATEMENTThe dentate gyrus (DG) has many important cognitive roles as well as being associated with affective behavior. This study addressed how a glutamatergic DG cell type called mossy cells (MCs) contributes to diverse behaviors, which is timely because it is known that MCs regulate the activity of the primary DG cell type, granule cells (GCs), but how MC activity influences behavior is unclear. We show, surprisingly, that activating MCs can lead to adverse behavioral outcomes, and inhibiting MCs have an opposite effect. Importantly, the results appeared to be task-dependent and showed that testing both sexes was important. Additional experiments indicated what MC and GC circuitry was involved. Taken together, the results suggest how MCs influence behaviors that involve the DG.

show abstract

Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation

Cited by 95 publications

References 61 publications

Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors

Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors

Neuromodulation of hippocampal long-term synaptic plasticity

Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice

Contact Info

Product

Resources

About