Korean J Physiol Pharmacol.  2012 Feb;16(1):65-70. 10.4196/kjpp.2012.16.1.65.

Developmental Switch of the Serotonergic Role in the Induction of Synaptic Long-term Potentiation in the Rat Visual Cortex

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

• KMID: 2285442
• DOI: http://doi.org/10.4196/kjpp.2012.16.1.65

Abstract

Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-week-old rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-HT2 receptors, but not by the activation of either 5-HT1A or 5-HT3 receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

Keyword

5-HT; SSRI; Citalopram; 5-HT2 receptor; Para-chloroamphetamine

MeSH Terms

Adult
Aging
Animals
Brain
Citalopram
Critical Period (Psychology)
Depression
Dominance, Ocular
Fluoxetine
Humans
Long-Term Potentiation
N-Methylaspartate
p-Chloroamphetamine
Plastics
Rats
Receptors, Serotonin, 5-HT3
Serotonin
Visual Cortex
Citalopram
Fluoxetine
N-Methylaspartate
Plastics
Receptors, Serotonin, 5-HT3
Serotonin
p-Chloroamphetamine

Figure

• 

  Fig. 1 Switching effect of 5-HT on the induction of LTP in the rat visual cortex. (A) The effect of the TBS of layer 4 (indicated with arrow) on layer 2/3 FP in control slices (open circle, n=10) and in 5-HT-perfused slices (closed circle, n=10) from 5-week-old rats. The right panel shows the representative average traces in a slice marked with corresponding symbols, which were taken at the time period indicated with corresponding numbers. Scales represent 0.4 mV and 2 ms, respectively. (B) The effect of the TBS of layer 4 (indicated with arrow) on layer 2/3 FP in control slices (open circle, n=11) and in 5-HT-perfused slices (closed circle, n=12) from 8-week-old rats. The right panel shows the representative average traces in a slice marked with corresponding symbols, which were taken at the time period indicated with corresponding numbers. Scales represent 0.4 mV and 2 ms, respectively. (C) Age-dependent inhibition and facilitation of layer 2/3 LTP induction induced by TBS to layer 4 in the rat visual cortex. Numbers of the experiments are from 5 to 12. **p<0.01 and ***p<0.001 compared with the corresponding control.

• 

  Fig. 2 Effect of endogenous 5-HT on the induction of LTP in 8-week-old rats. (A) Average response to TBS applied at the indicated time (arrow) in PCA-incubated (open circle, n=5) and citalopram-treated slices (closed circle, n=6). Insets show the average FP recording taken from a representative experiment at the indicated time period with corresponding numbers. Scales represent 0.4 mV and 2 ms, respectively. (B) Summary plot of the LTP induction in PCA- and citalopram-treated slices from 8-week-old rats (n=5 and n=6, respectively). *p<0.05 compared with the baseline.

• 

  Fig. 3 Effect of 5-HT receptor antagonists and agonists on the induction of LTP in 8-week-old rats. (A) The effect of 5-HT receptor antagonists on layer 2/3 LTP induced by TBS to layer 4 (indicated with arrow) in 8-week-old rats. NAN-190 (10 µM, n=7, open triangle), mesulergine (10 µM, n=6, closed circle) and Y-25130 (10 µM, n=5, open square) were co-applied into the bath with 5-HT (10 µM). The right panel shows the representative average traces in a slice marked with corresponding symbols, which were taken at the time period indicated with corresponding numbers. Scales represent 0.4 mV and 2 ms, respectively. (B) The effect of 5-HT receptor agonists on layer 2/3 LTP induced by TBS to layer 4 (indicated with arrow) in 8-week-old rats. 8-OH-DPAT (10 µM, n=7, open triangle), DOI (10 µM, n=7, closed circle) and 2-me-5-HT (10 µM, n=7, open square) were applied into the bath throughout the experiment. The right panel shows the representative average traces in a slice marked with corresponding symbols, which were taken at the time period indicated with corresponding numbers. Scales represent 0.4 mV and 2 ms, respectively. (C) Summary plot of the effect of antagonists for 5-HT receptor subtypes. *p<0.05 and ***p<0.001 compared with the baseline. (D) Summary plot of the effect of agonists for 5-HT receptor subtypes. *p<0.05 compared with the baseline.

• 

  Fig. 4 Effect of 5-HT2 receptor antagonists and a agonist on the 5-HT facilitation of LTP induction in 8-week-old rats. (A) The effect of 5-HT2 receptor antagonists and agonists on layer 2/3 LTP induced by TBS to layer 4 (indicated with arrow) in 8-week-old rats. MDL 11939 (10 µM, n=5, closed circle), MDL 11939 (10 nM, n=11, open circle), and SB 242084 (5 µM, n=5, closed square) were co-applied into the bath with 5-HT (10 µM). WAY 161503 (10 µM, n=8, gray triangle) was applied without 5-HT into the bath. The right panel shows the representative average traces in a slice marked with corresponding symbols, which were taken at the time period indicated with corresponding numbers. Scales represent 0.4 mV and 2 ms, respectively. (B) Summary plot of the effect of antagonists and a agonist for 5-HT2 receptors. *p<0.05 and ***p< 0.001 compared with the baseline.

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