Effects of Serotonin on the Induction of Long-term Depression in the Rat Visual Cortex

Abstract

Long-term potentiation (LTP) and long-term depression (LTD) have both been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. In a previous study, we suggested that a developmental increase in serotonin [5-hydroxytryptamine (5-HT)] might be involved in the decline of LTP, since 5-HT inhibited its induction. In the present study, to further understand the role of 5-HT in a developmental decrease in plasticity, we investigated the effect of 5-HT on the induction of LTD in the pathway from layer 4 to layer 2/3. LTD was inhibited by 5-HT (10 μM) in 5-week-old rats. The inhibitory effect was mediated by activation of 5-HT2 receptors. Since 5-HT also regulates the development of visual cortical circuits, we also investigated the role of 5-HT on the development of inhibition. The development of inhibition was retarded by chronic (2 weeks) depletion of endogenous 5-HT in 5-week-old rats, in which LTD was reinstated. These results suggest that 5-HT regulates the induction of LTD directly via activation of 5-HT2 receptors and indirectly by regulating cortical development. Thus, the present study provides significant insight into the roles of 5-HT on the development of visual cortical circuits and on the age-dependent decline of long-term synaptic plasticity.

The Development of Phasic and Tonic Inhibition in the Rat Visual Cortex

“…Since the relative strength of inhibition compared with excitation is more important than the development itself [28], we investigated the development of phasic inhibition relative to the same amount of excitation in different age groups. We found a developmental increase in the inhibitory-to-excitatory ratio (I/E ratio), which confirmed our previous findings [11]. Inhibition increased during post-natal development from 3 to 8 weeks and reached a plateau at 8 weeks of age.…”

“…In a previous study, we reported the development of synaptically evoked phasic inhibition during the critical period from 3 to 5 weeks of age in the rat visual cortex [11]. To further evaluate the development of inhibition, in the present study we extended the time period to 12 weeks of age.…”

“…Since inhibition matures during postnatal development of the visual cortex [8,9], the effect of inhibition on these processes changes during development, and thus inhibitory maturation exerts its effect on the functional development of the visual cortex. For example, whereas inhibitory influence over a certain threshold level is necessary for the induction of long-term synaptic plasticity at the early postnatal developmental stage [10], further development of inhibition suppresses the induction of plasticity [6,11]. Furthermore, the kinetic features of inhibition are known to change during development of the visual cortex [12].…”

Differential modulation of phasic and tonic inhibition underlies serotonergic suppression of long-term potentiation in the rat visual cortex

“…In the visual cortex, 5-HT regulates the development of phasic inhibition (Jang et al, 2010), and the induction of long-term synaptic plasticity (Kim et al, 2006;Moreau et al, 2013) and ocular dominance (OD) plasticity (Gu and Singer, 1995 Since GABAergic inhibition is also critically involved in the regulation of long-term synaptic plasticity (Jang et al, 2009) and OD plasticity (Hensch et al, 1998), 5-HT signaling on GABAergic inhibition has been of particular interest. Although we previously reported that 5-HT enhances phasic inhibition (Jang et al, 2012), it is largely unknown whether 5-HT affects tonic inhibition in the visual cortex and in other brain regions.…”

Layer-specific serotonergic facilitation of IPSC in layer 2/3 pyramidal neurons of the visual cortex

“…In the visual cortex, the expression of 5-HT receptor subtypes also changes during postnatal development in cats (Kojic et al 2000) and rats (Li et al 2004), which implies that 5-HT may exert different functions during the lifespan. For example, whereas 5-HT facilitated the induction of long-term potentiation (LTP) in the visual cortex of adult rats (Vetencourt et al 2008), it was also involved in the age-dependent decline of N-methyl-D-aspartate (NMDA) receptor-dependent LTP (Edagawa et al 2001;Kim et al 2006) and long-term depression (LTD) (Jang et al 2010) during the critical period (postnatal 3-5 wk in rat visual cortex).…”