Biomedical subjects

Mary J Palmer

Publications and source records attributed to Mary J Palmer.

7 recordsLinked to original sources

PubMed2006

Functional segregation of synaptic GABAA and GABAC receptors in goldfish bipolar cell terminals.

The transmission of light responses to retinal ganglion cells is regulated by inhibitory input from amacrine cells to bipolar cell (BC) synaptic terminals. GABA(A) and GABA(C) receptors in BC terminals mediate currents with different kinetics and are likely to have distinct functions in limiting BC output; however, the synaptic properties and localization of the receptors are currently poorly understood. By recording endogenous GABA receptor currents directly from BC terminals in goldfish retinal slices, I show that spontaneous GABA release activates rapid GABA(A) receptor miniature inhibitory postsynaptic currents (mIPSCs) (predominant decay time constant (tau(decay)), 1.0 ms) in addition to a tonic GABA(C) receptor current. The GABA(C) receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) has no effect on the amplitude or kinetics of the rapid GABA(A) mIPSCs. In addition, inhibition of the GAT-1 GABA transporter, which strongly regulates GABA(C) receptor currents in BC terminals, fails to reveal a GABA(C) component in the mIPSCs. These data suggest that GABA(A) and GABA(C) receptors are highly unlikely to be synaptically colocalized. Using non-stationary noise analysis of the mIPSCs, I estimate that GABA(A) receptors in BC terminals have a single-channel conductance (gamma) of 17 pS and that an average of just seven receptors mediates a quantal event. From noise analysis of the tonic current, GABA(C) receptor gamma is estimated to be 4 pS. Identified GABA(C) receptor mIPSCs exhibit a slow decay (tau(decay), 54 ms) and are mediated by approximately 42 receptors. The distinct properties and localization of synaptic GABA(A) and GABA(C) receptors in BC terminals are likely to facilitate their specific roles in regulating the transmission of light responses in the retina.

Animals↗

PubMed2006

Modulation of Ca(2+)-activated K+ currents and Ca(2+)-dependent action potentials by exocytosis in goldfish bipolar cell terminals.

Retinal bipolar cells convey light-evoked potentials from photoreceptors to ganglion cells and mediate the initial stages of visual signal processing. They do not fire Na(+)-dependent action potentials (APs) but the Mb1 class of goldfish bipolar cell exhibits Ca(2+)-dependent APs and regenerative potentials that originate in the axon terminal. I have examined the properties of Ca(2+)-dependent APs in isolated bipolar-cell terminals in goldfish retinal slices. All recorded terminals fired spontaneous or evoked APs at frequencies of up to 15 Hz. When an AP waveform was used as a voltage stimulus, exocytosis was evoked by single APs, maintained throughout AP trains and modulated by AP frequency. Furthermore, feedback inhibition of the Ca2+ current (I(Ca)) by released vesicular protons reduced depression of exocytosis during AP trains. In the absence of K+ current inhibition, step depolarizations and AP waveforms evoked a rapidly activated outward current that was dependent on Ca2+ influx I(K(Ca). I therefore investigated whether proton-mediated feedback inhibition of I(Ca) affected the activation of I(K(Ca)). A transient inhibition of I(K(Ca)) was observed that was dependent on exocytosis, blocked by high-pH extracellular buffer, of similar magnitude to inhibition of I(Ca) but occurred with a delay of 2.7 ms. In addition, the amplitude of APs evoked under current clamp was inhibited by the action of vesicular protons released by the APs. Protons released via exocytosis may therefore be a significant modulator of Ca(2+)-dependent currents and regenerative potentials in bipolar-cell terminals.

Action Potentials↗

PubMed2004

Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity.

BACKGROUND: Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP) and its counterpart long-term depression (LTD) of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP. RESULTS: We find that when LTP involves an increase in unitary conductance, subsequent depotentiation invariably involves the return of unitary conductance to pre-LTP values. In contrast, when LTP does not involve a change in unitary conductance then depotentiation also occurs in the absence of any change in unitary conductance, indicating a reduction in the number of activated receptors as the most likely mechanism. CONCLUSIONS: These data show that unitary conductance can be bi-directionally modified by synaptic activity. Furthermore, there are at least two distinct mechanisms to restore synaptic strength from a potentiated state, which depend upon the mechanism of the previous potentiation.

Animals↗

PubMed2004

Multiple, developmentally regulated expression mechanisms of long-term potentiation at CA1 synapses.

Long-term potentiation (LTP) of AMPA receptor-mediated synaptic transmission at hippocampal CA1 synapses has been extensively studied, but the mechanisms responsible for its expression remain unresolved. We tested a hypothesis that there are multiple, developmentally regulated expression mechanisms by directly comparing LTP in hippocampal slices obtained from rats of two ages. At postnatal day 12 (P12), LTP was fully accounted for by an increase in potency (mean amplitude of responses excluding failures). This was associated with either an increase in AMPA receptor single-channel conductance (gamma) or no change in gamma, suggesting an increase in the number of AMPA receptors. At P6, LTP was explained by an additional two mechanisms. In the majority of neurons, LTP was associated with an increase in success rate and a decrease in paired-pulse facilitation. In the remaining neurons, LTP was attributable to an increase in potency. However, in contrast to P12 neurons, the potency increase was associated with a decrease in gamma, suggesting the insertion of receptors with lower gamma. We conclude that there are multiple expression mechanisms for LTP at CA1 synapses that are developmentally regulated. These findings suggest that a single class of synapse uses a number of different molecular mechanisms to produce long-term changes in synaptic strength.

Animals↗

PubMed2003

Synaptic cleft acidification and modulation of short-term depression by exocytosed protons in retinal bipolar cells.

The release of vesicular protons during exocytosis causes a feedback inhibition of Ca2+ channels in photoreceptor terminals; however, the effect of this inhibition on subsequent exocytosis has not been studied. Here we show that a similar L-type Ca2+ channel inhibition occurs in bipolar cell terminals in slices of goldfish retina, and we investigate the effect that this has on subsequent exocytosis with membrane capacitance measurements. We find that transient Ca2+ current inhibition is correlated with exocytosis and modulated by the concentration of extracellular pH buffer. Ca2+ current inhibition is negligible in acutely dissociated terminals, demonstrating the importance of an intact synaptic cleft. The sensitivity of bipolar cell Ca2+ currents to extracellular pH was assessed: channel conductance is reduced and activation is shifted to more positive potentials by acidification. The effect of Ca2+ current inhibition on subsequent exocytosis was investigated by measuring paired-pulse depression. Under conditions in which there is a large amount of inhibition of Ca2+ influx, the degree of paired-pulse depression is significantly reduced. Finally, we show that under physiological (bicarbonate) buffering conditions, pronounced Ca2+ current inhibition occurs after exocytosis ( approximately 60% peak inhibition), which can decrease subsequent exocytosis during single depolarizations. We estimate that exocytosis is accompanied by a transient change in synaptic cleft pH from 7.5 to approximately 6.9. We suggest that this effect serves as an activity-dependent modulator of exocytosis at ribbon-type synapses where a large and compact coterie of vesicles can fuse at each active zone.

Animals↗

PubMed2003

Synaptic activation of presynaptic glutamate transporter currents in nerve terminals.

Glutamate uptake by high-affinity transporters is responsible for limiting the activation of postsynaptic receptors and maintaining low levels of ambient glutamate. The reuptake process generates membrane currents, which can be activated by synaptically released glutamate in glial cells and some postsynaptic neurons. However, less is known about presynaptic transporter currents because the small size of synaptic boutons precludes direct recordings. Here, we have recorded from two giant nerve terminals: bipolar cell synaptic terminals in goldfish retina and the calyx of Held in rat auditory brainstem. Exocytosis was evoked by brief depolarizations and measured as an increase in membrane capacitance. In isolated bipolar cell terminals, exocytosis was associated with an anion (NO3- or Cl-) current. The current peaked 2.8 msec after the start of the depolarization and decayed with a mean time constant of 8.5 msec. It was inhibited by the nontransportable glutamate transporter antagonist sc-threo-beta-benzyloxyaspartate (TBOA) but was insensitive to the GLT1/EAAT2 subtype-selective antagonist dihydrokainate and was affected by extracellular pH buffering. A TBOA-sensitive anion current was also evoked by application of exogenous glutamate to bipolar cell terminals. The large single-channel conductance, derived from noise analysis, and previous immunolocalization studies suggest that synaptically released glutamate activates EAAT5-type transporters in bipolar cell terminals. In contrast, neither exocytosis nor exogenous glutamate evoked a transporter current in the calyx of Held. Glutamate transporter currents with rapid kinetics are therefore identified and characterized in bipolar cell terminals, providing a valuable system for investigating the function and modulation of presynaptic glutamate transporters.

Amino Acid Transport System X-AG↗

PubMed2002

Phasic transmitter release from tonic neurons.

Graded and prolonged presynaptic depolarizations trigger the tonic release of neurotransmitters from sensory neurons. In this issue of Neuron, Simmons reports that postsynaptic responses of locust interneuron synpapses are determined by the rate rather than the amplitude of presynaptic depolarization, suggesting a mechanism for increasing the signaling capabilities of this synapse with respect to visual processing.

Animals↗