Korean J Physiol Pharmacol.  2010 Oct;14(5):337-343. 10.4196/kjpp.2010.14.5.337.

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

• Jang HJ
• Cho KH
• Park SW
• Kim MJ
• Yoon SH
• Rhie DJ

• KMID: 2071703
• DOI: http://doi.org/10.4196/kjpp.2010.14.5.337

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 micrometer) 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.

Keyword

5-HT; Development; GABA; Inhibition; LTD; Synaptic plasticity; Visual cortex

MeSH Terms

Animals
Depression
Dominance, Ocular
gamma-Aminobutyric Acid
Long-Term Potentiation
Plastics
Rats
Serotonin
Visual Cortex
Plastics
Serotonin
gamma-Aminobutyric Acid

Figure

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  Fig. 1. Inhibitory effect of 5-HT on the induction of LTD. (A) Effect of 5-HT on the induction of LTD in 3-week-old rats. Low-frequency stimulation (LFS) with 0.2-msec square pulses was applied to induce LTD under normal ACSF (open circle, ‘0.2 ms Con,’ n=5) and in the presence of 5-HT (10 μM, closed circle, ‘0.2 ms + 5-HT,’ n=9). LTD was also induced by stimulation with 0.1-msec square pulses (open square, ‘0.1 ms Con,’ n=5; closed square, ‘0.1 ms + 5-HT,’ n=9; respectively). Right panel plots individual data (symbols) and averages (thick solid lines). ∗p<0.05 vs. ‘Con’ for each stimulus pulse duration. (B) LFS with stimulus pulse duration of 0.2-msec was applied to the slices from 5-week-old rats (open circle, ‘0.2 ms Con,’ n=5). Concentration-dependent responses were obtained with four different concentrations of 5-HT at 0.01 μM (closed square, n=7), 0.1 μM (closed triangle, n=7), 1 μM (closed circle, n=8), and 10 μM (closed diamond, n=8). Right panel plots individual data (symbols) and averages (thick solid lines). ∗p<0.05 and ∗∗p<0.01 vs. ‘0.2 ms Con’. (C) Concentration-inhibition curve for the effect of 5-HT. The curve was fitted by sigmoid function (IC50=1.3 μM). Insets show average traces taken from a representative experiment at the indicated period.

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  Fig. 2. Effects of 5-HT receptor subtype-specific agonists and antagonists on the induction of LTD. LFS was applied with the stimulus duration of 0.2-msec to the slices from 5-week-old rats. (A) LFS was applied in the presence of 8-OH-DPAT (10 μM) (closed circle, ‘DPAT,’ n=10) or 5-HT (10 μM) + NAN-190 (10 μM) (open circle, ‘5-HT + NAN,’ n=7). (B) LFS was applied in the presence of DOI (10 μM) (closed circle, ‘DOI,’ n=9), 5-HT (10 μM) + mesulergine (10 μM) (open circle, ‘5-HT + Mes,’ n=7) or 5-HT (10 μM) + ketanserin (10 μM) (open square, ‘5-HT + Ket,’ n=8). (C) LFS was applied in the presence of 2-me-5-HT (30 μM) (closed circle, ‘2-me-5-HT,’ n=7). Insets show average traces taken from a representative experiment at the indicated period. Right panels plot individual data (symbols) and averages (thick solid lines). ∗p<0.05 and ∗∗p<0.01 vs. the baseline response.

• 

  Fig. 3. Effect of 5-HT depletion on the induction of LTD. Slices from 5-week-old rats were incubated in PCA (10 μM)-containing solution for 2 hours to deplete 5-HT acutely and then LFS was applied with 0.1-msec stimulation duration (closed circle, ‘acute PCA,’ n=9). To investigate the effect of chronic depletion of 5-HT, LFS was applied to the slices from 5-week-old rats, in which 5-HT was depleted for 2 weeks by intraperitoneal injection of PCA (8 mg/kg) (open square, ‘chronic PCA,’ n=10). Insets show average traces taken from a representative experiment at the indicated periods. Right panel plots individual data (symbols) and averages (thick solid lines). ∗∗∗p<0.001 vs. the baseline response.

• 

  Fig. 4. Effect of chronic 5-HT depletion on the development of the inhibitory network. 5-HT was depleted by single intraperitoneal injection of PCA (8 mg/kg) at 3 weeks of age and slices were taken at 5 weeks of age. (A) Experimental sequences. 20 mV of post-synaptic potential (PSP) and corresponding postsynaptic current (PSC) were recorded at –75 mV of membrane potential (left traces). Bath application of DNQX (20 μM) and APV (50 μM) eliminated PSP and PSC (center traces). At 0 mV of membrane potential, isolated inhibitory postsynaptic potential (IPSP) and current (IPSC) were recorded (right traces). CC: current clamp mode; VC: voltage clamp mode. (B) Averaged IPSPs (upper traces) and IPSCs (lower traces) showing differences between groups. Left traces: IPSPs and IPSCs recorded from slices of 3-week-old (thin line, n=8) and 5-week-old rats (thick line, n=8). Center traces: from slices of 5-week-old (thick line) and 5-week-old PCA-injected (thin line, n=8) rats. Right traces: from slices of 5-week-old rats (thick line) and slices of 5-week-old rats in which 5-HT was depleted by PCA incubation for 2 hours (thin line, n=8). (C) Individual data (symbols) and averages (thick lines) for PSP, PSC, IPSP and IPSC for each of the groups indicated in the lower panels. ∗p<0.05, ∗∗p<0.01, and ∗∗∗p<0.001 between groups linked by lines.

Reference

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