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

Abstract

Jang HJ, Cho KH, Park SW, Kim MJ, Yoon SH, Rhie DJ. Layer-specific serotonergic facilitation of IPSC in layer 2/3 pyramidal neurons of the visual cortex. J Neurophysiol 107: 407-416, 2012. First published October 19, 2011 doi:10.1152/jn.00535.2011 inhibits the induction of longterm synaptic plasticity in layer 2/3 of the visual cortex at the end of its critical period in rats. However, the cellular and molecular mechanisms remain unclear. Since inhibitory influence is crucial in the induction of synaptic plasticity, the effect of 5-HT on inhibitory transmission was investigated in layer 2/3 pyramidal neurons of the primary visual cortex. The amplitude of inhibitory postsynaptic current (IPSC), but not excitatory postsynaptic current, evoked by stimulation of the underlying layer 4, was increased by ϳ20% with a bath application of 5-HT. The amplitude of miniature IPSC was also increased by the application of 5-HT, while the paired-pulse ratio was not changed. The facilitating effect of 5-HT on IPSC was mediated by the activation of 5-HT 2 receptors. An increase in intracellular Ca 2ϩ via release from inositol 1,4,5-trisphosphate (IP 3 )-sensitive stores, which was confirmed by confocal Ca 2ϩ imaging, and activation of Ca 2ϩ /calmodulin-dependent kinase II (CaMKII) were involved in the facilitation of IPSC by 5-HT. However, 5-HT failed to facilitate IPSC evoked by the stimulation of layer 1. These results suggest that activation of 5-HT 2 receptors releases intracellular Ca 2ϩ via IP 3 -sensitive stores, which facilitates GABA A ergic transmission via the activation of CaMKII in layer 2/3 pyramidal neurons of the visual cortex in a layer-specific manner. Thus facilitation of inhibitory transmission by 5-HT might be involved in regulating the information flow and the induction of long-term synaptic plasticity, in a pathwayspecific manner.␥-aminobutyric acid; inhibitory transmission; 5-HT; CaMKII; IP 3 SEROTONIN (5-hydroxytryptamine, 5-HT), one of the major neuromodulators in the brain, has been implicated in many brain functions, such as memory, mood disorders, sleep, neuroendocrine control, sex behavior, feeding behavior, and epilepsy. The molecular mechanisms of 5-HT functions are diverse because of its multiple receptor subtypes (Barnes and Sharp 1999), and thus the cellular functions might differ depending on the cellular expression of receptor subtypes in different brain areas. In the visual cortex, the expression of 5-HT receptor subtypes also changes during postnatal development in cats (Kojic et al.

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

“…1) and in our previous study (Jang et al, 2012). Bicuculline at the concentration of 300 nM could reverse the $20% increase in IPSCs by 5-HT (data not shown).…”

“…In our previous study on 5-HT regulation of IPSC (Jang et al, 2012), we noticed that 5-HT also affects holding currents as well as IPSCs. This suggested that 5-HT might also regulate tonic GABA A R currents.…”

“…For the regulation of both phasic and tonic inhibition, phosphorylation of pre-and postsynaptic molecules could all be involved. In our previous study, we concluded that the increase in phasic inhibition depends mainly on postsynaptic factors, since PPR did not change and the inclusion of CaMKII inhibitor and Ca 2+ chelator in the pipette occluded the increase (Jang et al, 2012). When tonic inhibition is modified, the changes in the level of ambient GABA should be considered first (Glykys and Mody, 2007).…”

“…3C). We previously reported that the increase in IPSC by the activation of 5-HT 2 receptor was mediated by Ca 2+ from the internal store and CaMKII (Jang et al, 2012). Inclusion of the CaMKII inhibitor in the pipette solution prevented the 5-HT-mediated increase in sIPSC (37.22 ± 1.93 pA to 35.94 ± 1.94 pA, n = 11, P = 0.067) but holding currents were diminished (4.43 ± 1.1 pA, P < 0.01) (Fig.…”

“…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. Because phasic and tonic inhibition might regulate cellular excitability cooperatively, the action of neuromodulators on phasic and tonic inhibition should be studied concurrently to understand the functional implications of the two modes of inhibition in the regulation of neuronal activity.…”