Abstract
Major depression and schizophrenia are associated with dysfunctions of serotoninergic and dopaminergic systems mainly in the prefrontal cortex (PFC). Both serotonin and dopamine are known to modulate synaptic plasticity. 5-HT1A receptors (5-HT1ARs) and dopaminergic type D1 receptors are highly represented on dendritic spines of layer 5 pyramidal neurons (L5PyNs) in PFC. How these receptors interact to tune plasticity is poorly understood. Here we show that D1-like receptors (D1Rs) activation requires functional 5HT1ARs to facilitate LTP induction at the expense of LTD. Using 129/Sv and 5-HT1AR-KO mice, we recorded post-synaptic currents evoked by electrical stimulation in layer 2/3 after activation or inhibition of D1Rs. High frequency stimulation resulted in the induction of LTP, LTD or no plasticity. The D1 agonist markedly enhanced the NMDA current in 129/Sv mice and the percentage of L5PyNs displaying LTP was enhanced whereas LTD was reduced. In 5-HT1AR-KO mice, the D1 agonist failed to increase the NMDA current and orientated the plasticity towards L5PyNs displaying LTD, thus revealing a prominent role of 5-HT1ARs in dopamine-induced modulation of plasticity. Our data suggest that in pathological situation where 5-HT1ARs expression varies, dopaminergic treatment used for its ability to increase LTP could turn to be less and less effective.
Highlights
The prefrontal cortex (PFC) is a critical region of the brain that controls many cognitive functions such as working memory [1], social behavior [2] and decision making [3]
In a previous work in the PFC, we showed that theta burst firing induced either longterm potentiation (LTP), long-term depression (LTD) or no plasticity of responses evoked by layer 2/3 stimulation and recorded in layer 5 pyramidal neurons (L5PyNs) and this distribution of plasticity is modulated towards LTD by 5-HT1ARs activation [17]
DA and 5-HT coexist in the PFC [59,60] and 5-HT1ARs are involved in the modulation of dopaminergic activity [42]
Summary
The prefrontal cortex (PFC) is a critical region of the brain that controls many cognitive functions such as working memory [1], social behavior [2] and decision making [3]. This does not alter the authors adherence to PLOS ONE policies on sharing data and materials. These modulations of neuronal activity are known to be under the control of various neurotransmitters such as serotonin (5-HT) and dopamine (DA). Dysfunction of these mechanisms are observed in many neurological disorders, including schizophrenia [5], bipolar disorder [5], attention deficit/hyperactivity disorder [6] and Alzheimer’s disease [7]
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