Spontaneous Postsynaptic Potentials Research Articles

2-Deoxy-D-Glucose Exhibits Anti-seizure Effects by Mediating the Netrin-G1-KATP Signaling Pathway in Epilepsy.

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been reported to exert antiepileptic effects by upregulating KATP subunits (kir6.1 and kir6.2). We evaluated whether 2-DG exhibits anti-seizure effect by mediating the netrin-G1-KATP signaling pathway in epilepsy. In a mouse epilepsy model induced by lithium chloride-pilocarpine, 2-DG intervention increased the mRNA and protein expression levels of kir6.1 and kir6.2, and these increases were significantly reversed after knocking down netrin-G1 expression. Similarly, in cultured neurons with a magnesium-free medium, we found that the frequency of spontaneous postsynaptic potentials (SP) was increased, and in the meanwhile, expression levels of kir6.1 and kir6.2 were increased after pretreatment with 2DG. These effects were remarkably reversed after knocking down netrin-G1. Thus, our findings show that 2DG exhibits anti-seizure effects through the netrin-G1-KATP signaling pathway.

Mitochondrial Dysregulation and Impaired Autophagy in iPSC-Derived Dopaminergic Neurons of Multiple System Atrophy.

SummaryMultiple system atrophy (MSA) is a progressive neurodegenerative disease that affects several areas of the CNS, whose pathogenesis is still widely unclear and for which an effective treatment is lacking. We have generated induced pluripotent stem cell-derived dopaminergic neurons from four MSA patients and four healthy controls and from two monozygotic twins discordant for the disease. In this model, we have demonstrated an aberrant autophagic flow and a mitochondrial dysregulation involving respiratory chain activity, mitochondrial content, and CoQ10 biosynthesis. These defective mechanisms may contribute to the onset of the disease, representing potential therapeutic targets.

Ciberial Muscle 9 (CM9) Electrophysiological Recordings in Adult Drosophila melanogaster.

The complexity surrounding presynaptic recordings in mammals is a significant barrier to the study of presynaptic mechanisms during neurotransmission in the mammalian central nervous system (CNS). Here we describe an adult fly neuromuscular junction (NMJ), the ciberial muscle 9 (CM9) NMJ, which allows for the recording of both evoked (EPSPs) and spontaneous postsynaptic excitatory potentials (mEPSPs) at a mature glutamatergic synapse. Combined with CM9-specific genetic technologies, the CM9 NMJ provides a powerful experimental system to better understand the regulation of neurotransmitter release at a mature synapse.

Presynaptic serotonergic modulation of spontaneous and miniature synaptic activity in frog lumbar motoneurons

In this study we investigated the effect of 5-HT on the spontaneous and miniature synaptic activity in lumbar motoneurons from isolated frog spinal cord using intracellular recording. 5-HT increased the frequency of the spontaneous and miniature postsynaptic potentials (mPSPs). The effect of 5-HT on different subpopulations of mPSPs was multidirectional: it increased the frequency of glutamatergic excitatoty mPSP by 18 % and decreased the frequency of glycinergic inhibitory mPSP by 28 %, but had no effect on the frequency of GABAergic inhibitory mPSP. The amplitude and kinetic parameters of any subpopulation of mPSPs did not change. The data obtained show that 5-HT regulates the probability of glutamate and glycine release from presynaptic terminals ending at the frog spinal motoneurons. 5-HT shifts the ba- lance between synaptic excitation and inhibition in the spinal neural network toward excitation. Thus, 5-HT participates in control of motor output and provides its facilitation.

Calcitonin gene-related peptide increases acetylcholine quantal size in neuromuscular junctions of mice

We used an intracellular microelectrode technique to study the mechanisms of action of two isoforms (human and rat) of calcitonin gene-related peptide (CGRP) on the evoked and spontaneous quantal secretion of acetylcholine (ACh) in mouse diaphragm motor synapses. Recordings of miniature endplate potentials (MEPPs) and evoked multiquantal endplate potentials (EPPs) in a cut neuromuscular preparation showed that CGRP increased the amplitude of EPPs without influencing their quantal content. Both isoforms of CGRP in a wide range of concentrations (1nM–1μM) provoked a similar considerable increase in MEPPs amplitude in a dose-dependent manner (up to 150–160% compared to control) without changing their frequency, rise-time, and decay. Inhibition of CGRP-receptors by truncated CGRP (CGRP8-37) completely prevented the potentiating effect of CGRP on the MEPPs amplitude. The effect of CGRP was not accompanied by changes in input resistance of muscle fiber membrane but was fully prevented by inhibition of vesicular ACh transport by vesamicol. Inhibition of protein kinase A (PKA) by H-89 also prevented CGRP action on the MEPPs amplitude. It is concluded that, in mammalian neuromuscular junctions, different isoforms of exogenously applied CGRP uniformly potentiate amplitudes of evoked and spontaneous postsynaptic potentials acting presynaptically via an increase in ACh quantal size.

Activity-dependent scaling of GABAergic excitation by dynamic Cl− changes in Cajal–Retzius cells

To unravel the functional implications of activity-dependent Cl- changes during early stages of neuronal development, we determined which changes in the GABA reversal potential (E (GABA)) and GABAergic rheobase shifts were induced by episodes of GABA(A) receptor activation using gramicidin-perforated patch-clamp recordings from Cajal-Retzius cells in tangential cortical slices of newborn mice. Under this condition, focal application of the GABA(A) agonist muscimol (10 μM) depolarized the membrane by 15 ± 0.8 mV (n = 35). Such subthreshold GABAergic depolarizations considerably reduced the rheobase, corresponding to an excitatory action. After repetitive focal muscimol applications (50 pulses at 0.5 Hz) a significant reduction of E (GABA) and an attenuation of the excitatory GABAergic rheobase shift were observed, while the GABAergic membrane conductance and the absolute value of the rheobase were unaltered after the muscimol pulses. Bath application of 100 μM carbachol induced bursts of spontaneous GABAergic postsynaptic potentials. Both, E (GABA) and the excitatory GABAergic rheobase shift was significantly reduced after such barrage of carbachol-induced GABAergic postsynaptic potentials, while neither the GABAergic membrane conductance nor the absolute value of the rheobase was affected under this condition. Both results indicate that GABAergic activity itself can limit the excitatory effects of GABA(A) receptor activation, which supports the hypothesis that the low capacity of the Cl- homeostasis in immature neurons could be a substrate for synaptic scaling and homeostatic plasticity.

Selective changes in inhibition as determinants for limited hyperexcitability in the insular cortex of epileptic rats

The insular cortex (IC) is involved in the generalization of epileptic discharges in temporal lobe epilepsy (TLE), whereas seizures originating in the IC can mimic the epileptic phenotype seen in some patients with TLE. However, few studies have addressed the changes occurring in the IC in TLE animal models. Here, we analyzed the immunohistochemical and electrophysiological properties of IC networks in non-epileptic control and pilocarpine-treated epileptic rats. Neurons identified with a neuron-specific nuclear protein antibody showed similar counts in the two types of tissue but parvalbumin- and neuropeptide Y-positive interneurons were significantly decreased (parvalbumin, approximately -35%; neuropeptide Y, approximately -38%; P < 0.01) in the epileptic IC. Non-adapting neurons were seen more frequently in the epileptic IC during intracellular injection of depolarizing current pulses. In addition, single-shock electrical stimuli elicited network-driven epileptiform responses in 87% of epileptic and 22% of non-epileptic control neurons (P < 0.01) but spontaneous postsynaptic potentials had similar amplitude, duration and intervals of occurrence in the two groups. Finally, pharmacologically isolated, GABA(A) receptor-mediated inhibitory postsynaptic potentials had more negative reversal potential (P < 0.01) and higher peak conductance (P < 0.05) in epileptic tissue. These data reveal moderate increased network excitability in the IC of pilocarpine-treated epileptic rats. We propose that this limited degree of hyperexcitability originates from the loss of parvalbumin- and neuropeptide Y-positive interneurons that is compensated by an increased drive for GABA(A) receptor-mediated inhibition.

Neural phosphoproteomics of a chronic hypoxia model—Lymnaea stagnalis

Chronic hypoxia is a common clinical event that induces adaptive responses and can result in behavioral deterioration. The reduction of metabolic rate during hypoxia may limit overall protein phosphorylation owing to the lack of high energy phosphate. However, the hypoxia-induced regulation of phosphoproteins is poorly understood. Here, we characterized the CNS phosphoproteome of Lymnaea stagnalis, a freshwater snail that has been used as a model to study chronic hypoxia-induced neural depression. After hypoxia treatment for 4 days, the motor behavior of the snail was suppressed. Electrophysiological measurements from Pedal A (PeA) interneurons showed that hypoxia increased the frequency of spontaneous postsynaptic excitatory potentials (sEPSPs), but reduced the firing frequency, the amplitude, and the half-width duration (APD50) of spontaneous action potentials. Imaging with a fluorescent phosphate label, Pro-Q Diamond, revealed that the neuronal phosphoprotein level was reduced after the hypoxia treatment. The hypoxia-induced changes in the phosphoproteome of the central ganglia were quantified using one-dimensional gel-electrophoresis by comparing the fluorescence intensity ratio of phospholabeled phosphoproteins versus total proteins between the hypoxia and control groups. We analyzed 16 protein bands: eight showed decreased phosphorylation levels after hypoxia treatment, and eight did not change. Using mass spectrometry analysis and protein database matching we found three phosphoproteins that may be associated with chronic hypoxia-induced neuronal adaptive response of the snail. This is the first proteomic screening for neural phosphoproteins in chronic hypoxia.

Semi-loose seal Neurobiotin electroporation for combined structural and functional analysis of neurons

Intracellular sharp-electrode, whole-cell patch clamp and juxtacellular labeling methods have previously been developed for combined analysis of neuronal structure and function. We describe a novel electroporation technique for labeling neurons with Neurobiotin, using patch electrodes in a semi-loose seal configuration (R = 100-300 MOmega) with very small amplitude pulses (50 mV). The addition of 2% Neurobiotin to the intracellular solution in the patch electrode reduces the dielectric membrane breakdown voltage threshold by about threefold. The resulting pore formation allows for (1) the stable recording of spontaneous and light-evoked postsynaptic potentials without significant cytoplasmic washout and (2) the passage of dye without spillover. The efficiency and reliability of the method makes it particularly suitable for the serial recording and labeling of multiple neurons in a small area of tissue.

Network hyperexcitability within the deep layers of the pilocarpine‐treated rat entorhinal cortex

In this study we report that in the presence of normal buffer, epileptiform discharges occur spontaneously (duration = 2.60 +/- 0.49 s) or can be induced by electrical stimuli (duration = 2.50 +/- 0.62 s) in the entorhinal cortex (EC) of brain slices obtained from pilocarpine-treated rats but not in those from age-matched, nonepileptic control (NEC) animals. These network-driven epileptiform events consist of field oscillatory sequences at frequencies greater than 200 Hz that most often initiate in the lateral EC and propagate to the medial EC with 4-63 ms delays. The NMDA receptor antagonist CPP depresses the rate of occurrence (P < 0.01) of these spontaneous epileptiform discharges but fails in blocking them. Paradoxically, stimulus-induced epileptiform responses are enhanced in duration during CPP application. However, concomitant application of NMDA and non-NMDA glutamatergic antagonists abolishes spontaneous and stimulus-induced epileptiform events. Intracellular recordings from lateral EC layer V cells indicate a lower frequency of spontaneous hyperpolarizing postsynaptic potentials in pilocarpine-treated tissue than in NEC (P < 0.002) both under control conditions and with glutamatergic receptor blockade; the reversal potential of pharmacologically isolated GABA(A) receptor-mediated inhibitory postsynaptic potentials has similar values in the two types of tissue. Finally, immunohistochemical analysis shows that parvalbumin-positive interneurons are selectively reduced in number in EC deep layers. Collectively, these results indicate that reduced inhibition within the pilocarpine-treated EC layer V may promote network epileptic hyperexcitability.

Physiology and morphology of callosal projection neurons in mouse

In the mammalian neocortex, the corpus callosum serves as the major source of interhemispheric communication, composed of axons from callosal neurons located in supragranular (II/III) and infragranular (V/VI) layers. We sought to characterize the physiology and morphology of supragranular and infragranular callosal neurons in mice using retrograde tracers and whole-cell patch clamp recordings. Whole-cell patch clamp recordings were made from retrogradely labeled callosal neurons following unilateral injection of fluorescent latex microspheres in the contralateral sensory-motor cortex. Following recordings and biocytin dialysis, labeled neurons were reconstructed using computer-assisted camera lucida (Neurolucida) for morphological analyses. Whole-cell recordings revealed that callosal neurons in both supra- and infragranular layers display very similar intrinsic membrane properties and are characteristic regular-spiking neurons. Morphological features examined from biocytin-filled reconstructions as well as retrogradely BDA labeled cells did not reveal any differences. Analysis of spontaneous postsynaptic potentials from callosal neurons did reveal several differences including average amplitude, frequency, and decay time. These findings suggest that callosal neurons in both supra- and infragranular layers have similar phenotypes though belong to different local, intracortical networks.

Membrane Properties and Firing Patterns of Inferior Colliculus Neurons: An In Vivo Patch-Clamp Study in Rodents

The inferior colliculus (IC) is a large auditory nucleus in the midbrain, which is a nearly obligatory relay center for ascending auditory projections. We made in vivo whole cell patch-clamp recordings of IC cells in young-adult anesthetized C57/Bl6 mice and Wistar rats to characterize their membrane properties and spontaneous inputs. We observed spikelets in both rat (18%) and mouse (13%) IC neurons, suggesting that IC neurons may be connected by electrical synapses. In many cells, spontaneous postsynaptic potentials were sufficiently large to contribute to spike irregularity. Cells differed considerably in the number of simultaneous spontaneous postsynaptic potentials that would be needed to trigger an action potential. Depolarizing and hyperpolarizing current injections showed six different types of firing patterns: buildup, accelerating, burst-onset, burst-sustained, sustained, and accommodating. Their relative frequencies were similar in both species. In mice, about half of the cells showed a clear depolarizing sag, suggesting that they have the hyperpolarization-activated current I(h). This sag was observed more often in burst and in accommodating cells than in buildup, accelerating, or sustained neurons. Cells with I(h) had a significantly more depolarized resting membrane potential. They were more likely to fire rebound spikes and generally showed long-lasting afterhyperpolarizations following long depolarizations. We therefore suggest a separate functional role for I(h).

Neuronal precursors within the adult rat subventricular zone differentiate into dopaminergic neurons after substantia nigra lesion and chromaffin cell transplant

Neurogenesis in the adult mammalian brain continues in the subventricular zone (SVZ). Neuronal precursors from the SVZ migrate along the rostral migratory stream to replace olfactory bulb interneurons. After the destruction of the nigro-striatal pathway (SN-lesion), some SVZ precursors begin to express tyrosine hydroxylase (TH) and neuronal markers (NeuN). Grafting of chromaffin cells (CCs) into the denervated striatum increases the number of TH+ cells (SVZ TH+ cells; Arias-Carrión et al., 2004). This study examines the functional properties of these newly differentiating TH+ cells. Under whole-cell patch-clamp, most SVZ cells recorded from lesioned and grafted animals (either TH+ or TH-) were non-excitable. Nevertheless, a small percentage of SVZ TH+ cells had the electrophysiologic phenotype of mature dopaminergic neurons and showed spontaneous postsynaptic potentials. Dopamine (DA) release was measured in SVZ and striatum from both control and SN-lesioned rats. As expected, 12 weeks after SN lesion, DA release decreased drastically. Nevertheless, 8 weeks after CCs graft, release from the SVZ of SN-lesioned rats recovered, and even surpassed that from control SVZ, suggesting that newly formed SVZ TH+ cells release DA. This study shows for the first time that in response to SN-lesions and CC grafts neural precursors within the SVZ change their developmental program, by not only expressing TH, but more importantly by acquiring excitable properties of mature dopaminergic neurons. Additionally, the release of DA in a Ca(2+)-dependent manner and the attraction of synaptic afferents from neighboring neuronal networks gives further significance to the overall findings, whose potential importance is discussed.

Reactive Oxygen Species Mediate the Potentiating Effects of ATP on GABAergic Synaptic Transmission in the Immature Hippocampus

Reactive oxygen species (ROS) constitute important signaling molecules in the central nervous system. They regulate a number of different functions both under physiological conditions and under pathological conditions. Here we tested the hypothesis that in the immature hippocampus ATP, the most diffuse neurotransmitter in the brain, modulates synaptic transmission via ROS. We show that ATP, acting on metabotropic P2Y1 receptors, increased the frequency of GABA(A)-mediated spontaneous postsynaptic currents (SPSCs) in CA3 principal cells, an effect that was prevented by the antioxidant N-acetyl-cysteine or by catalase, an enzyme that breaks down H2O2. The effect of ATP on SPSCs was mimicked by H2O2 or by the pro-oxidant, Fe2+, which, through the Fentol reaction, catalyzes the conversion of H2O2 into highly reactive hydroxyl radicals. MRS-2179, a P2Y1 receptor antagonist, removed the facilitatory action of Fe2+ on SPSCs, suggesting that endogenous ATP acting on P2Y1 receptors is involved in Fe2+-induced modulation of synaptic transmission. Imaging ROS with the H2O2-sensitive dye DCF revealed that ATP induces generation of peroxide in astrocytes via activation of P2Y1 receptors coupled to intracellular calcium rise. Neither N-acetyl-cysteine nor catalase prevented Ca2+ transients induced by ATP in astrocytes. Since a single hippocampal astrocyte can contact many neurons, ATP-induced ROS signaling may control thousands of synapses. This may be crucial for information processing in the immature brain when GABAergic activity is essential for the proper wiring of the hippocampal network.

Cholesterol and synaptic transmitter release at crayfish neuromuscular junctions

During exocytosis of synaptic transmitters, the fusion of highly curved synaptic vesicle membranes with the relatively planar cell membrane requires the coordinated action of several proteins. The role of membrane lipids in the regulation of transmitter release is less well understood. Since it helps to control membrane fluidity, alteration of cholesterol content may alter the fusibility of membranes as well as the function of membrane proteins. We assayed the importance of cholesterol in transmitter release at crayfish neuromuscular junctions where action potentials can be measured in the preterminal axon. Methyl-beta-cyclodextrin (MbetaCD) depleted axons of cholesterol, as shown by reduced filipin labelling, and cholesterol was replenished by cholesterol-MbetaCD complex (Ch-MbetaCD). MbetaCD blocked evoked synaptic transmission. The lack of postsynaptic effects of MbetaCD on the time course and amplitude of spontaneous postsynaptic potentials or on muscle resting potential allowed us to focus on presynaptic mechanisms. Intracellular presynaptic axon recordings and focal extracellular recordings at individual boutons showed that failure of transmitter release was correlated with presynaptic hyperpolarization and failure of action potential propagation. All of these effects were reversed when cholesterol was replenished with Ch-MbetaCD. However, focal depolarization of presynaptic boutons and administration of a Ca2+ ionophore both triggered transmitter release after cholesterol depletion. Therefore, both presynaptic Ca2+ channels and Ca2+-dependent exocytosis functioned after cholesterol depletion. The frequency of spontaneous quantal transmitter release was increased by MbetaCD but recovered when cholesterol was reintroduced. The increase in spontaneous release was not through a calcium-dependent mechanism because it persisted with intense intracellular calcium chelation. In conclusion, cholesterol levels in the presynaptic membrane modulate several key properties of synaptic transmitter release.

Subiculum network excitability is increased in a rodent model of temporal lobe epilepsy

In this study, we used in vitro electrophysiology along with immunohistochemistry and molecular techniques to study the subiculum--a limbic structure that gates the information flow from and to the hippocampus--in pilocarpine-treated epileptic rats. Comparative data were obtained from age-matched nonepileptic controls (NEC). Subicular neurons in hippocampal-entorhinal cortex (EC) slices of epileptic rats were: (i) hyperexcitable when activated by CA1 or EC inputs; and (ii) generated spontaneous postsynaptic potentials at higher frequencies than NEC cells. Analysis of pharmacologically isolated, GABA(A) receptor-mediated inhibitory postsynaptic potentials revealed more positive reversal potentials in epileptic tissue (-67.8 +/- 6.3 mV, n = 16 vs. -74.8 +/- 3.6 mV in NEC, n = 13; P < 0.001) combined with a reduction in peak conductance (17.6 +/- 11.3 nS vs. 41.1 +/- 26.7 nS in NEC; P < 0.003). These electrophysiological data correlated in the epileptic subiculum with (i) reduced levels of mRNA expression and immunoreactivity of the neuron-specific potassium-chloride cotransporter 2; (ii) decreased number of parvalbumin-positive cells; and (iii) increased synaptophysin (a putative marker of sprouting) immunoreactivity. These findings identify an increase in network excitability within the subiculum of pilocarpine-treated, epileptic rats and point at a reduction in inhibition as an underlying mechanism.

Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

In this study we examined the developmental roles of acetylcholine (ACh) by establishing and analyzing mice lacking choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh. As predicted, ChAT-deficient embryos lack both spontaneous and nerve-evoked postsynaptic potentials in muscle and die at birth. In mutant embryos, abnormally increased nerve branching occurs on contact with muscle, and hyperinnervation continues throughout subsequent prenatal development. Postsynaptically, ACh receptor clusters are markedly increased in number and occupy a broader muscle territory in the mutants. Concomitantly, the mutants have significantly more motor neurons than normal. At an ultrastructural level, nerve terminals are smaller in mutant neuromuscular junctions, and they make fewer synaptic contacts to the postsynaptic muscle membrane, although all of the typical synaptic components are present in the mutant. These results indicate that ChAT is uniquely essential for the patterning and formation of mammalian neuromuscular synapses.

Cellular Mechanisms of Infralimbic and Prelimbic Prefrontal Cortical Inhibition and Dopaminergic Modulation of Basolateral Amygdala NeuronsIn Vivo

The basolateral amygdala (BLA) is believed to be involved in schizophrenia, depression, and other disorders that display affective components. The neuronal activity of the BLA, and BLA-mediated affective behaviors, are driven by sensory stimuli transmitted in part from sensory association cortical regions. These same behaviors may be regulated by prefrontal cortical (PFC) inputs to the BLA. However, it is unclear how two sets of glutamatergic inputs to the BLA can impose opposing actions on BLA-mediated behaviors; specifically, it is unclear how PFC inputs exert inhibitory actions over BLA projection neurons. Dopamine (DA) receptor activation enhances BLA-mediated behaviors. Although we have demonstrated that DA suppresses medial PFC inputs to the BLA and enhances sensory cortical inputs, the precise cellular mechanisms for its actions are unknown. In this study we use in vivo intracellular recordings to determine the means by which glutamatergic inputs from the PFC inhibit BLA projection neurons, contrast that with glutamatergic inputs from the association sensory cortex (Te3) that drive BLA projection neurons, and examine the effects of DA receptor activation on neuronal excitability, spontaneous postsynaptic potentials (PSPs), and PFC-evoked PSPs. We found that PFC stimulation inhibits BLA projection neurons by three mechanisms: chloride-mediated hyperpolarization, a persistent decrease in neuronal input resistance, and shunting of PSPs; all effects are possibly attributable to recruitment of inhibitory interneurons. DA receptor activation enhanced neuronal input resistance by a postsynaptic mechanism (via DA D2 receptors), suppressed spontaneously occurring and PFC-evoked PSPs (via DA D1 receptors), and enhanced Te3-evoked PSPs.

Mechanisms Underlying Developmental Changes in the Firing Patterns of ON and OFF Retinal Ganglion Cells during Refinement of their Central Projections

Patterned neuronal activity is implicated in the refinement of connectivity during development. Calcium-imaging studies of the immature ferret visual system demonstrated previously that functionally separate ON and OFF retinal ganglion cells (RGCs) develop distinct temporal patterns of spontaneous activity as their axonal projections undergo refinement. OFF RGCs become spontaneously more active compared with ON cells, resulting in a decrease in synchronous activity between these cell types. This change in ON and OFF activity patterns is suitable for driving the activity-dependent refinement of their axonal projections. Here, we used whole-cell and perforated-patch recording techniques to elucidate the mechanisms that underlie the developmental alteration in the ON and OFF RGC activity patterns. First, we show that before the refinement period, ON and OFF RGCs have similar spike patterns; however, during the period of segregation, OFF RGCs demonstrate significantly higher spike rates relative to ON cells. With increasing age, OFF cells require less depolarization to reach their action potential threshold and fire more spikes in response to current injection compared with ON cells. In addition, spontaneous postsynaptic currents and potentials are greater in magnitude in OFF cells than ON cells. In contrast, before axonal refinement, there are no differences in the intrinsic excitability or synaptic drive onto ON and OFF cells. Together, our results show that developmental changes in ON and OFF RGC excitability and in the strength of their synaptic drives act together to reshape the spike patterns of these cells in a manner appropriate for the refinement of their connectivity.

Potentiation of 5-HT 3 receptor functions in the hippocampal CA1 region of rats following repeated electroconvulsive shock treatments

Modulation of serotonin (5-HT) 3-receptor function by repeated electroconvulsive shock (ECS) treatment was investigated to elucidate the mechanism underlying the effectiveness of electroconvulsive therapy (ECT) which is clinically used for drug-resistant depression. ECS (100 V, 1 s) was applied once a day for 14 days via an electrode placed on the ears of rats (ECS group). For controls, rats were handled similar to the ECS-treated group except for the stimulation. Hippocampal slices (thickness, 450 μm) were prepared 24 h after the final ECS treatment when rats were 5–6 weeks old. Intracellular recordings were made from the neurons in the CA1 pyramidal cell layer. Activation of 5-HT 3 receptors increased spontaneous postsynaptic potentials (sPSP). Increased sPSP was mainly mediated by GABA. The 5-HT 3 receptor mediated increase in sPSP was potentiated in the ECS group compared with the control group. These findings suggest that the 5-HT 3 receptor function is potentiated by repeated ECS.