Extracellular glucose-dependent IPSC enhancement by leptin in fast-spiking to pyramidal neuron connections via JAK2-PI3K pathway in the rat insular cortex. (1st May 2019)

• Record Type: Journal Article
• Authors: Murayama, Shota; Yamamoto, Kiyofumi; Fujita, Satoshi; Takei, Hiroki; Inui, Tadashi; Ogiso, Bunnai; Kobayashi, Masayuki
• Is Part Of: Neuropharmacology. Volume 149(2019)
• Page Start: 133
• Page End: 148
• Publication Date: 2019-05-01
• Subjects: Cerebral cortex -- Tyrosine kinase receptor -- Release probability -- Gustation -- Ob-Rb; ACSF artificial cerebrospinal fluid -- AgRP agouti-related peptide -- AMPK adenosine monophosphate-activated protein kinase -- ARCH arcuate nucleus of the hypothalamus -- cDI caudal part of DI -- DI dysgranular IC -- FSN fast-spiking neuron -- IC insular cortex -- JAK2 janus kinase 2 -- MAPK mitogen-activated protein kinase -- MCA middle cerebral artery -- MC4R melanocortin 4 receptors -- NPY neuropeptide Y -- Ob-Rb leptin receptors -- PI3K phosphatidylinositol 3 kinase -- PKB/Akt protein kinase B -- PN pyramidal neuron -- POMC proopiomelanocortin -- PPR paired-pulse ratio -- rDI rostral part of DI -- RF rhinal fissure -- ROIs region of interests -- SHP2 SH2-containing protein tyrosine phosphatase 2 -- STAT3 signal transducer and activator of transcription 3 -- TRPC transient receptor potential C -- uEPSCs unitary excitatory postsynaptic currents -- uIPSCs unitary inhibitory postsynaptic currents -- VDCC voltage-dependent Ca2+ channel -- VGAT vesicular-GABA transporter; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.02.021
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Leptin is produced in the adipocytes and plays a pivotal role in regulation of energy balance by controlling appetite and metabolism. Leptin receptors are widely distributed in the brain, especially in the hypothalamus, hippocampus, and neocortex. The insular cortex (IC) processes gustatory and visceral information, which functionally correlate to feeding behavior. However, it is still an open issue whether and how leptin modulates IC neural activities. Our paired whole-cell patch-clamp recordings using IC slice preparations demonstrated that unitary inhibitory postsynaptic currents (uIPSCs) but not uEPSCs were potentiated by leptin in the connections between pyramidal (PNs) and fast-spiking neurons (FSNs). The leptin-induced increase in uIPSC amplitude was accompanied by a decrease in paired-pulse ratio. Under application of inhibitors of JAK2-PI3K but not MAPK pathway, leptin did not change uIPSC amplitude. Variance-mean analysis revealed that leptin increased the release probability but not the quantal size and the number of release site. These electrophysiological findings suggest that the leptin-induced uIPSC increase is mediated by activation of JAK2-PI3K pathway in presynaptic FSNs. An in vivo optical imaging revealed that leptin application decreased excitatory propagation in IC induced by electrical stimulation of IC. These leptin-induced effects were not observed under the low energy states: low glucose concentration (2.5 mM) in vitro and one-day-fasting condition in vivo . However, leptin enhanced uIPSCs under application of low glucose with an AMPK inhibitor. These results suggest that leptin suppresses IC excitation by facilitating GABA release in FSN→PN connections, which may not occur under a hunger state. Graphical abstract: Image 10976 Highlights: Leptin enhances unitary IPSCs (uIPSCs) but not uEPSCs in the rat cerebral cortex. Leptin-induced uIPSC enhancement is mediated via a presynaptic mechanism. JAK2 and PI3K-PKB/Akt pathways are involved in leptin-induced uIPSC enhancement. Leptin has no effect on uIPSCs/cortical excitation under a low glucose condition. AMPK is involved in leptin signaling under a low glucose condition.