Glutamate-activated currents in outside-out patches from spiny versus aspiny hilar neurons of rat hippocampal slices.

The desensitization rate of non-NMDA glutamate receptors was investigated in outside-out membrane patches obtained from morphologically identified spiny "mossy cells" (SMCs) and aspiny hilar interneurons (AHIs) in young rat hippocampal slices. The fast application of a 1 mM step of L-glutamate for 50-100 msec in the presence of TTX and dizolcipine (MK-801) onto patches excised from these neurons produced large glutamate-activated currents (GACs) that decayed with a single or double exponential time course despite the continued presence of agonist. These desensitization rates of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-sensitive receptors differed markedly between patches obtained from the two cell types. The fast time constant of desensitization in AHIs (n = 34) averaged 3.3 +/- 0.93 msec (mean +/- SD), while that of SMCs (n = 57) averaged 6.8 +/- 2.0 msec. Current-voltage relationships of the GACs did not differ between SMCs and AHIs, with comparable reversal potentials and no evidence of inward rectification. We also failed to observe significant Ca2+ permeability in either cell type. However, brief (< 1 msec) pulses of 1 mM glutamate produced rapidly decaying GACs with distinct kinetics in the two neuronal classes. Furthermore, analysis of the single glutamate-activated channel currents in outside-out patches from hilar neurons revealed a larger predominant single-channel current in AHIs versus SMCs. Lastly, we observed a greater sensitivity to cyclothiazide in SMCs versus AHIs, with half-maximal removal of desensitization being 90 mM and 200 mM, respectively. Taken together, these differences in GACs between SMCs and AHIs might indicate a functional correlate to the substantial heterogeneity in the molecular structure of glutamate receptor subunits or might be related to posttranslational modifications of these subunits, perhaps provided by the unique microenvironment in the spines covering SMCs.

Slower spontaneous excitatory postsynaptic currents in spiny versus aspiny hilar neurons.

In the hilar region of the rat hippocampus, large spontaneous excitatory postsynaptic currents (sEPSCs) mediated by non-NMDA glutamate receptors are present in both excitatory spiny mossy cells and inhibitory aspiny hilar interneurons, making these neurons ideal candidates for a comparative study using the tight seal whole-cell recording technique. Although sEPSCs have similar amplitude distributions, the rise and decay times are significantly slower in spiny versus aspiny neurons. Similar kinetic differences are observed in synaptic currents evoked by mossy fiber stimulation. These results demonstrate a physiological difference between the excitatory drive to excitatory and inhibitory neurons in the hilus that certainly contributes to differences in synaptic strength and that may be applicable to other brain regions. Furthermore, since the development or modification of individual spines or groups of spines may affect synaptic strength, these results may be pivotal in establishing a role for spines in modulating synaptic activity.

Comparison of pharmacological agents (aspartate vs. aminophosphonobutyric plus kynurenic acids) to block synaptic transmission from retinal photoreceptors in frog.

The combination of aminophosphonobutyric plus kynurenic acids (APB/Kyn) was compared to aspartate with respect to its ability to block synaptic transmission from photoreceptors. Like aspartate, APB/Kyn blocks photoreceptor synaptic transmission, as monitored by the b- and d-waves of the electroretinogram, by the proximal negative response and M-wave of the proximal retina, and by the light-evoked increase in extracellular K+ concentration in the inner plexiform layer. Unlike aspartate, APB/Kyn has relatively minor effects on retinal resistance, light-evoked changes in K+ and Ca2+ concentrations in the subretinal space, light-evoked changes in subretinal space volume, resting extracellular concentrations of K+ and Ca2+ in the proximal and distal retina, and the c-wave. Effects of APB/Kyn are generally more reversible than effects of Asp. A disadvantage of APB/Kyn is that the a-wave usually becomes smaller and slower. Overall, APB/Kyn disrupts the retina less than aspartate. Therefore, in some situations in which blockade of photoreceptor synaptic transmission is desired, the use of APB/Kyn may be preferable to that of aspartate.

Light-evoked changes in extracellular calcium concentration in frog retina.

Light-evoked changes in extracellular Ca2+ concentration were recorded with Ca2(+)-selective microelectrodes in the retina of the frog eyecup. A Ca-decrease at light onset and offset was found in the inner plexiform layer, and its properties are consistent with it resulting from Ca2+ influx into activated neuronal terminals. In the subretinal space, a Ca-increase at light onset and a Ca-decrease at offset were observed, and these likely arise directly from photoreceptors. A slower ON Ca-decrease was also seen here. Because it survives pharmacological isolation of the photoreceptors from post-synaptic interactions, but not physical isolation of the retina from the pigment epithelium, this component probably depends on pigment epithelial activity.