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GluA2-lacking, calcium-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) have unique properties, but their presence at excitatory synapses in pyramidal cells is controversial. We have tested certain predictions of the model that such receptors are present in CA1 cells and show here that the polyamine spermine, but not philanthotoxin, causes use-dependent inhibition of synaptically evoked excitatory responses in stratum radiatum, but not s. oriens, in cultured and acute hippocampal slices. Stimulation of single dendritic spines by photolytic release of caged glutamate induced an N-methyl-D-aspartate receptor-independent, use- and spermine-sensitive calcium influx only at apical spines in cultured slices. Bath application of glutamate also triggered a spermine-sensitive influx of cobalt into CA1 cell dendrites in s. radiatum. Responses of single apical, but not basal, spines to photostimulation displayed prominent paired-pulse facilitation (PPF) consistent with use-dependent relief of cytoplasmic polyamine block. Responses at apical dendrites were diminished, and PPF was increased, by spermine. Intracellular application of pep2m, which inhibits recycling of GluA2-containing AMPARs, reduced apical spine responses and increased PPF. We conclude that some calciumpermeable, polyamine-sensitive AMPARs, perhaps lacking GluA2 subunits, are present at synapses on apical dendrites of CA1 pyramidal cells, which may allow distinct forms of synaptic plasticity and computation at different sets of excitatory inputs. [ABSTRACT FROM AUTHOR]

In the mammalian central nervous system, the postsynaptic small-conductance Ca22+-dependent K+ (SK) channel has been shown to reduce postsynaptic depolarization and limit Ca2+ influx through N-methyl-D-aspartate receptors. To examine further the role of the postsynaptic SK channel in synaptic transmission, we studied its action at the Drosophila larval neuromuscular junction (NMJ). Repetitive synaptic stimulation produced an increase in postsynaptic membrane conductance leading to depression of excitatory postsynaptic potential amplitude and hyperpolarization of the resting membrane potential (RMP). This reduction in synaptic excitation was due to the postsynaptic Drosophila SK (dSK) channel; synaptic depression, increased membrane conductance and RMP hyperpolarization were reduced in dSK mutants or after expressing a Ca2+ buffer in the muscle. Ca2+ entering at the postsynaptic membrane was sufficient to activate dSK channels based upon studies in which the muscle membrane was voltage clamped to prevent opening voltage-dependent Ca2+ channels. Increasing external Ca2+ produced an increase in resting membrane conductance and RMP that was not seen in dSK mutants or after adding the glutamate-receptor blocker philanthotoxin. Thus it appeared that dSK channels were also activated by spontaneous transmitter release and played a role in setting membrane conductance and RMP. In mammals, dephosphorylation by protein phosphatase 2A (PP2A) increased the Ca2+ sensitivity of the SK channel; PP2A appeared to increase the sensitivity of the dSK channel since PP2A inhibitors reduced activation of the dSK channel by evoked synaptic activity or increased external Ca2. It is proposed that spontaneous and evoked transmitter release activate the postsynaptic dSK channel to limit synaptic excitation and stabilize synapses. [ABSTRACT FROM AUTHOR]

Auditory nerve fibers are the major source of excitation to the three groups of principal cells of the ventral cochlear nucleus (VCN), bushy, T stellate, and octopus cells. Shock-evoked excitatory postsynaptic currents (eEPSCs) in slices from mice showed systematic differences between groups of principal cells, indicating that target cells contribute to determining pre- and postsynaptic properties of synapses from spiral ganglion cells. Bushy cells likely to be small spherical bushy cells receive no more than three, most often two, excitatory inputs; those likely to be globular bushy cells receive at least four, most likely five, inputs. T stellate cells receive 6.5 inputs. Octopus cells receive >60 inputs. The N-methyl-d-aspartate (NMDA) components of eEPSCs were largest in T stellate, smaller in bushy, and smallest in octopus cells, and they were larger in neurons from younger than older mice. The average AMPA conductance of a unitary input is 22 ± 15 nS in both groups of bushy cells, <1.5 nS in octopus cells, and 4.6 ± 3 nS in T stellate cells. Sensitivity to philanthotoxin (PhTX) and rectification in the intracellular presence of spermine indicate that AMPA receptors that mediate eEPSCs in T stellate cells contain more GluR2 subunits than those in bushy and octopus cells. The AMPA components of eEPSCs were briefer in bushy (0.5 ms half-width) than in T stellate and octopus cells (0.8-0.9 ms half-width). Widening of eEPSCs in the presence of cyclothiazide (CTZ) indicates that desensitization shortens eEPSCs. CTZ-insensitive synaptic depression of the AMPA components was greater in bushy and octopus than in T stellate cells. [ABSTRACT FROM AUTHOR]

Horizontal cells (HCs) are inhibitory interneurons of the vertebrate retina. Unlike typical neurons, HCs are chronically depolarized in the dark, leading to a constant influx of Ca2+. Therefore, mechanisms of Ca2+ homeostasis in HCs must differ from neurons elsewhere in the central nervous system, which undergo excitotoxicity when they are chronically depolarized or stressed with Ca2+. HCs are especially well characterized in teleost fish and have been used to unlock mysteries of the vertebrate retina for over one century. More recently, mammalian models of the retina have been increasingly informative for HC physiology. We draw from both teleost and mammalian models in this review, using a comparative approach to examine what is known about Ca2+ pathways in vertebrate HCs. We begin with a survey of Ca2+-permeable ion channels, exchangers, and pumps and summarize Ca2+ influx and efflux pathways, buffering, and intracellular stores. This includes evidence for Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and N-methyl-d-aspartate receptors and for voltage-gated Ca2+ channels. Special attention is given to interactions between ion channels, to differences among species, and in which subtypes of HCs these channels have been found. We then discuss a number of unresolved issues pertaining to Ca2+ dynamics in HCs, including a potential role for Ca2+ in feedback to photoreceptors, the role for Ca2+-induced Ca2+ release, and the properties and functions of Ca2+-based action potentials. This review aims to highlight the unique Ca2+ dynamics in HCs, as these are inextricably tied to retinal function. [ABSTRACT FROM AUTHOR]

Schaffer collateral synapses in hippocampus show target-cell specific short-term plasticity. Using GFP-expressing Inhibitory Neuron (GIN) transgenic mice that express enhanced green fluorescent protein (EGFP) in a subset of somatostatin-containing interneurons (SOM interneurons), we previously showed that Schaffer collateral synapses onto SOM interneurons in stratum (S.) radiatum have unusually large (up to 6-fold) paired-pulse facilitation. This results from a low initial release probability and the enhancement of facilitation by synaptic activation of presynaptic kainate receptors. Here we further investigate the properties of these kainate receptors and examine their effects on short-term facilitation during physiologically derived stimulation patterns, using excitatory postsynaptic currents recorded in S. radiatum interneurons during Schaffer collateral stimulation in acute slices from juvenile GIN mice. We find that GluR5 and GluR6 antagonists decrease short-term facilitation at Schaffer collateral synapses onto SOM interneurons with no additive effects, suggesting that the presynaptic kainate receptors are heteromers containing both GluR5 and GluR6 subunits. The calcium-permeable receptor antagonist 1-napthyl acetyl spermine (NASPM) both mimics and occludes the effect of the kainate receptor antagonists, indicating that the presynaptic kainate receptors are calcium permeable. Furthermore, Schaffer collateral synapses onto SOM interneurons show up to 11-fold short-term facilitation during physiologically derived stimulus patterns, in contrast to other interneurons that have less than 1.5-fold facilitation. Blocking the kainate receptors reduces facilitation in SOM interneurons by ∼50% during the physiologically derived patterns and reduces the dynamic range. Activation of calcium-permeable kainate receptors containing GluR5/GluR6 causes a dramatic increase in short-term facilitation during physiologically derived stimulus patterns, a mechanism likely to be important in regulating the strength of Schaffer collateral synapses onto SOM interneurons in vivo. [ABSTRACT FROM AUTHOR]

Activity-dependent insertion of AMPA-type glutamate receptors is thought to underlie long-term potentiation (LTP) at Schaffer collateral fiber synapses on pyramidal cells in the hippocampal CA1 region. Although it is widely accepted that the AMPA receptors at these synapses contain glutamate receptor type 2 (GluR2) subunits, recent findings suggest that LTP in hippocampal slices obtained from 2- to 3-wk-old rodents is dependent on the transient postsynaptic insertion and activation of Ca2+-permeable, GluR2-lacking AMPA receptors. Here we examined whether LTP in slices prepared from adult animals exhibits similar properties. In contrast to previously reported findings, pausing synaptic stimulation for as long as 30 min post LTP induction had no effect on LTP maintenance in slices from 2- to 3-mo-old mice. LTP was also not disrupted by postinduction application of a selective blocker of GluR2-lacking AMPA receptors or the broad-spectrum glutamate receptor antagonist kynurenate. Although these results suggest that the role of GluR2-lacking AMPA receptors in LTP might be regulated during postnatal development, LTP in slices obtained from 15- to 21-day-old mice also did not require postinduction synaptic stimulation or activation of GluR2-lacking AMPA receptors. Thus the insertion and activation of GluR2-lacking AMPA receptors do not appear to be fundamental processes involved in LTP at excitatory synapses in the hippocampal CA1 region. [ABSTRACT FROM AUTHOR]