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Diana L Pettit

Publications and source records attributed to Diana L Pettit.

3 recordsLinked to original sources

Synaptic kainate currents reset interneuron firing phase.

Hippocampal interneuron activity has been linked to epileptogenesis, seizures and the oscillatory synaptic activity detected in behaving rats. Interneurons fire at specific times in the rhythmic cycles that comprise these oscillations; however, the mechanisms controlling these firing patterns remain unclear. We have examined the role of synaptic input in modulating the firing of spontaneously active rat hippocampal interneurons. We find that synaptic glutamate receptor currents of 20-30 pA increase instantaneous firing frequency and reset the phase of spontaneously firing CA1 stratum oriens interneurons. Kainate receptor (KAR)-mediated currents are particularly effective at producing this phase reset, while AMPA receptor currents are relatively ineffective. The efficacy of KAR-mediated currents is probably due to their 3-fold longer decay. Given the small amplitude of the currents needed for this phase reset, coincident activation of only a few KAR-containing synapses could synchronize firing in groups of interneurons. These data suggest that KARs are potent modulators of circuit behaviour and their activation alters hippocampal interneuron output.

Action Potentials↗

Variable kainate receptor distributions of oriens interneurons.

Interneuron kainate receptor (KAR) activation regulates normal network activity and modulates cell excitability. As a result, determining the subcellular distribution of KARs in a cell-specific manner is a necessary step toward understanding their role in network function. We have functionally mapped synaptic and extrasynaptic dendritic KARs on hippocampal oriens interneurons using local photolysis of caged glutamate. We find that the majority of trilaminar and oriens lacunosum-moleculare (O-LM) cells have uniform and continuous current densities along the lengths of their dendrites. However, there is a subpopulation of interneurons that have no KAR currents or currents exclusively at "hot spots" on the soma and dendrites. Finally, bistratified cells have KAR currents on all dendrites except those extending into the stratum radiatum. Thus KARs are functionally distributed in a cell-specific and cell-independent manner that may reflect the physiologically distinct roles they play in the hippocampal network.

Animals↗

Protein kinase A regulates calcium permeability of NMDA receptors.

Calcium (Ca2+) influx through NMDA receptors (NMDARs) is essential for synaptogenesis, experience-dependent synaptic remodeling and plasticity. The NMDAR-mediated rise in postsynaptic Ca2+ activates a network of kinases and phosphatases that promote persistent changes in synaptic strength, such as long-term potentiation (LTP). Here we show that the Ca2+ permeability of neuronal NMDARs is under the control of the cyclic AMP-protein kinase A (cAMP-PKA) signaling cascade. PKA blockers reduced the relative fractional Ca2+ influx through NMDARs as determined by reversal potential shift analysis and by a combination of electrical recording and Ca2+ influx measurements in rat hippocampal neurons in culture and hippocampal slices from mice. In slices, PKA blockers markedly inhibited NMDAR-mediated Ca2+ rises in activated dendritic spines, with no significant effect on synaptic current. Consistent with this, PKA blockers depressed the early phase of NMDAR-dependent LTP at hippocampal Schaffer collateral-CA1 (Sch-CA1) synapses. Our data link PKA-dependent synaptic plasticity to Ca2+ signaling in spines and thus provide a new mechanism whereby PKA regulates the induction of LTP.

Animals↗