5-HT-dependent synaptic plasticity of the prefrontal cortex in postnatal development

Abstract

Important functions of the prefrontal cortex (PFC) are established during early life, when neurons exhibit enhanced synaptic plasticity and synaptogenesis. This developmental stage drives the organization of cortical connectivity, responsible for establishing behavioral patterns. Serotonin (5-HT) emerges among the most significant factors that modulate brain activity during postnatal development. In the PFC, activated 5-HT receptors modify neuronal excitability and interact with intracellular signaling involved in synaptic modifications, thus suggesting that 5-HT might participate in early postnatal plasticity. To test this hypothesis, we employed intracellular electrophysiological recordings of PFC layer 5 neurons to study the modulatory effects of 5-HT on plasticity induced by theta-burst stimulation (TBS) in two postnatal periods of rats. Our results indicate that 5-HT is essential for TBS to result in synaptic changes during the third postnatal week, but not later. TBS coupled with 5-HT2A or 5-HT1A and 5-HT7 receptors stimulation leads to long-term depression (LTD). On the other hand, TBS and synergic activation of 5-HT1A, 5-HT2A, and 5-HT7 receptors lead to long-term potentiation (LTP). Finally, we also show that 5-HT dependent synaptic plasticity of the PFC is impaired in animals that are exposed to early-life chronic stress.

Maternal fluoxetine impairs synaptic transmission and plasticity in the medial prefrontal cortex and alters the structure and function of dorsal raphe nucleus neurons in offspring mice

“…Postnatal exposure to citalopram resulted in reduced expression of 5-HT transporter in rat cortex (Maciag et al, 2006). Since 5-HT receptors modulate glutamatergic transmission and neuronal membrane excitability (Higa et al, 2022; Zhong et al, 2008a, b), if similar effects occur in mice exposed to FLX, they might contribute to alterations in the induction of long-term synaptic plasticity observed in our experiments. In earlier studies aimed at finding facilitatory effects of 5-HT on the induction of LTD in mPFC slices, a higher concentration of 5-HT was used (40-50 μM), which markedly reduced evoked responses upon application (Higa et al, 2022; Zhong et al, 2008a, b).…”

“…It has been shown that FLX can transfer to the fetus through the placenta, and has also been found in breast milk (Heikkinen et al, 2003, Kim et al, 2006). During brain development 5-HT acts as a main modulator of neuronal proliferation, migration, differentiation, synaptic plasticity, and apoptotic cell death (reviewed in: Higa et al, 2022; Teissier et al, 2015; Vitalis and Parnavelas, 2003). Thus, FLX-induced increase in tissue 5- HT content may interfere with the normal development of brain circuitry (reviewed in: Adjimann et al, 2021).…”

Potential Anti-Amnesic Activity of a Novel Multimodal Derivative of Salicylamide, JJGW08, in Mice

“…Serotonergic neurons are widely distributed in the brain with high density in the hippocampus and prefrontal cortex, areas strongly associated with cognition [ 54 , 55 , 56 ] and depression [ 57 ]. Thus, it is unsurprising that serotonin and its receptors play a significant role in learning and memory processes, as well as mood regulation.…”

Advances in Alzheimer’s disease’s pharmacological treatment

“…Lately, serotonin receptors emerged as targets in cognitive impairment and AD ( Hung and Fu, 2017 ; Andrews et al, 2018 ; Kucwaj-Brysz et al, 2021 ; Solas et al, 2021 ; Higa et al, 2022 ). 5-HT6R and 5-HT7R are the most studied serotonin receptors in this scenario due to their brain distribution and noteworthy cognitive properties in vivo ( Kucwaj-Brysz et al, 2021 ).…”