Abstract
SummaryThe hippocampal mossy fiber (MF) synapse has been implicated in the pathophysiology and treatment of psychiatric disorders. Alterations of dopaminergic and serotonergic modulations at this synapse are candidate mechanisms underlying antidepressant and other related treatments. However, these monoaminergic modulations share the intracellular signaling pathway at the MF synapse, which implies redundancy in their functions. We here show that endogenous monoamines can potentiate MF synaptic transmission in mouse hippocampal slices by activating the serotonin 5-HT4 receptor. Dopamine receptors were not effectively activated by endogenous agonists, suggesting that the dopaminergic modulation is latent. Electroconvulsive treatment enhanced the 5-HT4 receptor-mediated serotonergic synaptic potentiation specifically at the MF synapse, increased the hippocampal serotonin content, and produced an anxiolytic-like behavioral effect in a 5-HT4 receptor-dependent manner. These results suggest that serotonin plays a predominant role in monoaminergic modulations at the MF synapse. Augmentation of this serotonergic modulation may mediate anxiolytic effects of electroconvulsive treatment.
Highlights
The hippocampal dentate gyrus and its mossy fiber (MF) output have been implicated in the pathophysiology of neuropsychiatric disorders and in their therapeutic treatments (Kobayashi, 2009; DeCarolis and Eisch, 2010; Tavitian et al, 2019)
We here show that endogenous monoamines can potentiate MF synaptic transmission in mouse hippocampal slices by activating the serotonin 5-HT4 receptor
Electroconvulsive treatment enhanced the 5-HT4 receptor-mediated serotonergic synaptic potentiation at the MF synapse, increased the hippocampal serotonin content, and produced an anxiolytic-like behavioral effect in a 5-HT4 receptor-dependent manner. These results suggest that serotonin plays a predominant role in monoaminergic modulations at the MF synapse
Summary
The hippocampal dentate gyrus and its mossy fiber (MF) output have been implicated in the pathophysiology of neuropsychiatric disorders and in their therapeutic treatments (Kobayashi, 2009; DeCarolis and Eisch, 2010; Tavitian et al, 2019). Serotonin and dopamine induce robust potentiation of the MF synaptic transmission (Kobayashi and Suzuki, 2007; Kobayashi et al, 2008) These monoaminergic modulations show marked alterations after antidepressant drug administration or ECT in mice (Kobayashi et al, 2008, 2010; 2012, 2013; 2017) and in mouse models of neuropsychiatric disorders including schizophrenia and epilepsy (Kobayashi et al, 2011b; Ohira et al, 2013; Shin et al, 2013), suggesting possible roles in both therapeutic treatments and pathophysiology of neuropsychiatric disorders. The functional meaning or the mode of operation of this redundant neuromodulatory system in physiological and pathological conditions remains to be elucidated
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