Presynaptic Interneuron Subtype- and Age-Dependent Modulation of GABAergic Synaptic Transmission by β-Adrenoceptors in Rat Insular Cortex

Abstract

beta-Adrenoceptors play a crucial role in the regulation of taste aversion learning in the insular cortex (IC). However, beta-adrenergic effects on inhibitory synaptic transmission mediated by gamma-aminobutyric acid (GABA) remain unknown. To elucidate the mechanisms of beta-adrenergic modulation of inhibitory synaptic transmission, we performed paired whole cell patch-clamp recordings from layer V GABAergic interneurons and pyramidal cells of rat IC aged from postnatal day 17 (PD17) to PD46 and examined the effects of isoproterenol, a beta-adrenoceptor agonist, on unitary inhibitory postsynaptic currents (uIPSCs). Isoproterenol (100 microM) induced facilitating effects on uIPSCs in 33.3% of cell pairs accompanied by decreases in coefficient of variation (CV) of the first uIPSC amplitude and paired-pulse ratio (PPR) of the second to first uIPSC amplitude, whereas 35.9% of pairs showed suppressive effects of isoproterenol on uIPSC amplitude obtained from fast spiking (FS) to pyramidal cell pairs. Facilitatory effects of isoproterenol were frequently observed in FS-pyramidal cell pairs at > or =PD24. On the other hand, isoproterenol suppressed uIPSC amplitude by 52.3 and 39.8% in low-threshold spike (LTS)-pyramidal and late spiking (LS)-pyramidal cell pairs, respectively, with increases in CV and PPR. The isoproterenol-induced suppressive effects were blocked by preapplication of 100 microM propranolol, a beta-adrenoceptor antagonist. There was no significant correlation between age and changes of uIPSCs in LTS-/LS-pyramidal cell pairs. These results suggest the presence of differential mechanisms in presynaptic GABA release and/or postsynaptic GABA(A) receptor-related assemblies among interneuron subtypes. Age- and interneuron subtype-specific beta-adrenergic modulation of IPSCs may contribute to experience-dependent plasticity in the IC.

Postsynaptic Cell Type–Dependent Cholinergic Regulation of GABAergic Synaptic Transmission in Rat Insular Cortex

“…uIPSCs were almost completely diminished by bath application of bicuculline methiodide (10 M), indicating that uIPSCs were mediated by GABA A receptors as previously demonstrated (Koyanagi et al 2010). Figure 1 shows a typical example of the effects of carbachol on uIPSCs.…”

“…The techniques for preparing and maintaining rat cortical slices in vitro were similar to those described previously (Koyanagi et al 2010). Briefly, vesicular GABA transporter (VGAT)-Venus line A transgenic rats (Nagai et al 2002 ;Uematsu et al 2008) of either sex aged from postnatal day 16 (PD16) to PD44 were deeply anesthetized with sodium pentobarbital (75 mg/kg, administered intraperitoneally) and decapitated.…”

“…FS cells were characterized by their low input resistance, short duration of action potential and AHP, and high frequency of repetitive firing ( Fig. 1B; Kawaguchi and Kubota 1997; Kobayashi et al 2008;Koyanagi et al 2010;Xiang et al 1998Xiang et al , 2002. Table 1 summarizes electrophysiological properties of IC interneurons, including the resting membrane potential, input resistance, single action potential, and repetitive firing.…”

“…Since ␤-adrenoceptor modulation of uIPSC amplitude is age dependent in the IC (Koyanagi et al 2010), there is a possibility that the effects of carbachol were age dependent. To explore this possibility, correlation between the normalized amplitude of uIPSCs during carbachol application and age was examined.…”

Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats

“…It can be speculated that clenbuterol suppresses GABAergic transmission, which likely originates from certain interneuron subtypes that primarily target layer 2/3 pyramidal cells, e.g., late spiking and low-threshold spiking interneurons. The GABAergic inputs to pyramidal cells from these interneuron subtypes have been proposed to be suppressed by b-AR activation (Koyanagi et al 2010). Furthermore, clenbuterol suppression of GABAergic transmission can be reversed by the selective b2-AR antagonist ICI118,551 (Fig.…”