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Lucia Cadetti "Kinetics of synaptic glutamate release from rod and cone terminals."

Abstract :


Light responses of cones and cone-driven neurons are faster than light responses of rods and rod-driven cells.
The faster light responses of cone-driven neurons relative to rod-driven neurons are supported by faster synaptic transmission in the cone pathway. Where do kinetic differences in synaptic transmission from rods and cones originate? To address this question, we used paired simultaneous recordings from photoreceptors and second-order neurons in the salamander retina. Depolarizing steps applied to photoreceptors evoked sustained calcium currents (ICa) in rods and cones that in turn stimulate transient excitatory postsynaptic currents (EPSCs) in horizontal and OFF bipolar cells. Consistent with faster synaptic transmission from cones, cone-driven EPSCs rose and decayed faster than rod-driven EPSCs, even when comparing inputs from a rod and cone onto the same postsynaptic neuron. Rod-cone differences in EPSCs therefore reflect properties of individual rod and cone synapses and do not originate in different second order cells. The possibility of different glutamate receptors at rod and cone synapses (e.g., slower KA receptors at rod synapses and faster AMPA receptors at cone synapses) was excluded by experiments using selective AMPA and KA agonists and antagonists which showed that rods and cones both contact pharmacologically similar AMPA receptors. Rod/cone differences in EPSC kinetics also cannot be explained by kinetics of activation and inactivation of ICa which are similar in both rods and cones. However, measurements of exocytosis showed profound differences in release kinetics at rod and cone synaptic terminals. Using two complementary techniques to measure exocytosis (simultaneous paired whole cell recordings and capacitance measurements of exocytosis), we found that exocytosis from both rods and cones involved an initial fast component of release and a slower sustained component. In cones, the initial fast component of release was more than tenfold faster than in rods (3 ms vs. 50 ms). To examine how release kinetics shape the EPSC, we convolved mEPSC waveforms with these empirically determined release functions for rods and cones. The predicted EPSC waveform closely matched the actual EPSC evoked by cones. Convolution with the rod release function also produced a good match in rod-driven cells, although the actual EPSC was often slower than the predicted EPSC, a discrepancy partly explained by rod-rod coupling. Thus, presynaptic release kinetics explains the transient waveform of the EPSC and largely accounts for rod and cone differences in EPSC kinetics. Calcium-induced calcium release (CICR) from intracellular calcium stores has been shown to be more prominent in rods than cones (Krizaj et al, 2003). We find that CICR plays an important role in making the rod-driven EPSC more sustained. However, blocking CICR with ryanodine does not render rod-driven EPSCs as fast as cone-driven EPSCs nor does it produce fast cone-like release kinetics. 

Selected publications

Cadetti L, Bryson EJ, Ciccone CA, Rabl K, Thoreson WB.
Calcium-induced calcium release in rod photoreceptor terminals boosts synaptic transmission during maintained depolarization.

Eur J Neurosci. 2006 Jun;23(11):2983-90.

Rabl K, Cadetti L, Thoreson WB.
Paired-pulse depression at photoreceptor synapses.

J Neurosci. 2006 Mar 1;26(9):2555-63.

Cadetti L, Thoreson WB.
Feedback effects of horizontal cell membrane potential on cone calcium currents studied with simultaneous recordings.
J Neurophysiol. 2006 Mar;95(3):1992-5. Epub 2005 Dec 21.

Cadetti L, Tranchina D, Thoreson WB.
A comparison of release kinetics and glutamate receptor properties in shaping rod-cone differences in EPSC kinetics in the salamander retina.

J Physiol. 2005 Dec 15;569(Pt 3):773-88. Epub 2005 Oct 13.

Jean Pierre Mothet