Abstract
Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.
Highlights
Serotonin, one of the most widely spread neurotransmitters in the central nervous system, has been known to play a critical role in brain morphogenesis and functions (Azmitia, 2001; Gaspar et al, 2004)
As the staining results showed, the length of basal dendrites of pyramidal cells was significantly shortened (Figure 2), and the number and density of dendritic spines were significantly reduced in Serotonin transporter (SERT) KO mice (Figure 3), suggesting that the ability of pyramidal cells to receive input information was decreased, which might cause less sensitivity to sound response (Figure 5)
The reduction of the length, the number, and density of dendritic spines in inhibitory interneurons of SERT KO mice suggests that the reduced inhibitory of the interneurons might cause less frequency selectivity of neurons (Figure 6)
Summary
One of the most widely spread neurotransmitters in the central nervous system, has been known to play a critical role in brain morphogenesis and functions (Azmitia, 2001; Gaspar et al, 2004). The defects of serotonergic neurons are related to many psychiatric disorders, including depression, anxiety, and autism spectrum disorder (ASD) (Simpson et al, 2011). Acting as a key regulator of serotonergic activity, the serotonin transporter (SERT) is usually selected as the target of antidepressant treatments. SERT represents a potential mediator for anxiety- and depressionrelated behaviors. Chronic exposure to selective serotonin reuptake inhibitors (SSRIs) was reported to elicit hearing disorders, such as tinnitus (Kehrle et al, 2015; Pattyn et al, 2016), auditory hallucinations (Kogoj, 2014), and hearing loss (Blazer and Tucci, 2018).
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