Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo

BACKGROUND: In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions. METHODS: We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system. RESULTS: Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms. CONCLUSION: These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

Papel das sinapses elétricas em crises epilépticas / The role of eletrical synapses in epileptic seizures

INTRODUÇÃO: No sistema nervoso central a comunicação entre neurônios se realiza através de estruturas denominadas sinapses: elétricas ou químicas. As sinapses elétricas são formadas pela aproximação das membranas plasmáticas de dois neurônios formando estruturas chamadas junções comunicantes (gap junctions, do inglês). As junções comunicantes são compostas por seis subunidades da proteína conexina de cada membrana, formando poros que comunicam o citoplasma de células adjacentes e permitem a passagem de íons e pequenas moléculas. OBJETIVOS: A presente revisão pretende descrever e discutir os principais resultados que apontam para uma importante relação entre junções comunicantes e sincronia neuronal durante crises epilépticas. RESULTADOS E CONCLUSÃO: Quando um neurônio é despolarizado, este tipo de comunicação permite a rápida transferência iônica entre as células, promovendo alta sincronia neuronal. Recentemente, o papel das junções comunicantes na geração e propagação de descargas epilépticas tem sido estudado através do uso de diferentes modelos experimentais in vivo, in vitro e in silico (modelos computacionais).

INTRODUCTION: In the central nervous system, neuronal communication is accomplished by structures called synapses: electrical or chemical. Electrical synapses are formed by the apposition of plasmatic membranes at gap junctions and the interaction of connexin subunits from two neurons. At this site, connexin complexes create intercellular pores that communicate the cytoplasm of adjacent neurons and allow free flow of ions and small molecules. OBJECTIVE: In this review, we will present and discuss recent results showing the possible involvement of electrical synapses in the neuronal hypersynchronization during epileptic seizures. RESULTS AND CONCLUSION: When a neuron is depolarized, ions flow very rapidly from one cell to the other promoting high neuronal synchrony. More recently, the role of gap junctions in the generation and propagation of epileptic discharges has been investigated using combined approaches of in vivo, in vitro and in silico (computational) models.

Immunocytochemical Study on Synaptic Circuitry of Glycinergic Neurons in the Rat Retina / 대한해부학회지

The role of glycine as an inhibitory neurotransmitter is well established, and glycinergic neurons appear to play an important role in the mammalian retinae[Ikeda & Sheardown, 1983 ; Bolz et al., 1985]. Though it has been reported that certain conventional and displaced amacrine cells and a few of bipolar cells are consistently labeled with anti-glycine antiserum in the mammalian retinae so far[W ssle et al., 1986 ; Pourcho & Goebel, 1987 ; Davanger et al., 1991 ; Yoo & Chung, 1992], little has been studied on the synaptic circuitry of glycinergic neurons to clarify mechanism of its action in the visual processing of the mammalian retinae. This study was conducted to localize glycinergic neurons and to define their synaptic circuitry in the rat retina by immunocytochemical method using anti -glycine antiserum. The results were as follows : 1. Glycinergic neurons of the rat retina were conventional and displaced amacrine cells, interstitial cells and bipolar cells. 2. Glycinergic amacrine cells could be subdivided into two types, that is, A II amacrine cells and other amacrine cells, according to their ultrastructures. Glycinergic A II amacrine and other amacrine cell processes comprised postsynaptic dyad at the ribbon synapse of rod bipolar axon terminals in the sublamina b of the inner plexiform layer of the retina. Glycinprgic A II amacrine cell processes made gap junctions with axon terminals of unlabeled invaginating cone bipolar cells in the sublamina b, and made chemical synapses onto axon terminals of unlabeled flat cone bipolar cells and onto dendrites of ganglion cells in the sublamina a of the inner plexiform layer. In the sublamina b of the inner plexiform layer, g1ycinergic amacrine cell processes were postsynaptic to axon terminals of unlabeled invaginating cone bipolar cells, and made chemical output synapses onto axon terminals of unlabeled invaginating cone bipolar and rod bipolar cells and onto the dendrites of ganglion cells. Such cases that pre- and post-synaptic processes of glycinergic amacrine cell processes were non- glycinergic amacrine cell processes were frequently observed throughout the inner plexiform layer. In some cases, glycinergic amacrine cell processes receiving synaptic inputs from other glycinergic amacrine cell process made synaptic outputs onto the non-glycinergic or glycinergic amacrine cell processes. 3. Glycinergic bipolar cells could be subdivided into invaginating and flat cone bipolar cells. Postsynaptic dyads of cone bipolar cells at the ribbon synapses were non-glycinergic amacrine and amacrine cell processes, glycinergic amacrine and amacrine cell processes, glycinergic amacrine and non-glycinergic amacrine cell processes, and dendrite and dendrite of ganglion cells. These results demonstrate that [1] glycinergic A II amacrine cell receiving synaptic input from rod bipolar cells inhibit flat cone bipolar cells and OFF ganglion cells via chemical synapse, and excite ON cone bipolar cells via electrical synapse ; thereby visual information in the darkness can be transmitted to ON ganglion cells via ON cone bipolar cells, and [2] glycine released from glycinergic neurons inhibits directly ON and OFF ganglion cells or indirectly ON and OFF ganglion cells via non-glycinergic amacrine or bipolar cells.