Salvador Borges

Variation in GABA mini amplitude is the consequence of variation in transmitter concentration

Miniature postsynaptic currents (minis) in cultured retinal amacrine cells, as in other central neurons, show large variations in amplitude. To understand the origin of this variability, we have exploited a novel form of synapse in which pre- and postsynaptic receptors sample the same quantum of transmitter. At these synapses, mini amplitudes measured simultaneously in the 2 cells show a strong correlation, accounting for, on average, more than half of the variance in amplitude. Two pieces of evidence support the conclusion that variations in the amount of transmitter in different quanta underlie this correlation. First, diazepam, which enhances GABA binding, increases mini amplitude, implying therefore that transmitter concentration is not saturating. Second, we show that amplitude distributions from all cells, even those with a small number of release sites, have the same shape, implying that most or all variance is intrinsic to each release site.

Control of transmitter release from retinal amacrine cells by Ca2+ influx and efflux

Cultured retinal amacrine cells show quantal GABAergic synaptic transmission. Voltage clamping pre- and post-synaptic cells of an isolated pair has allowed us to examine the entry and removal of Ca2+ at synaptic terminals. Brief presynaptic Ca2+ currents elicit an initial postsynaptic current that probably reflects the roughly synchronous exocytosis of docked vesicles. Prolonged Ca2+ currents elicit an additional second phase of release whose time course can greatly exceed that of the presynaptic voltage step. The time course of this second phase reflects a sustained increase in cytosolic Ca2+ and is matched closely by the activity of the presynaptic Na-Ca exchanger, as revealed by an exchange current. Eliminating the activity of the exchanger by removal of external Na+ prolongs this second phase of transmission greatly. Because transmitter release at these synapses outlasts Ca+ channel opening, Na-Ca exchange plays a significant role in shaping transmission.

The lateral spread of signal between bipolar cells of the tiger salamander retina

When mapped with a small spot of light, the central receptive fields of bipolar cells in the salamander retina are much larger than the extent of bipolar cell dendrites. Furthermore responses of bipolar cells to distant spots of light are considerably delayed relative to proximal spots. Using quantitative modelling, electrical coupling between bipolar cells is examined and rejected as a sufficient explanation of the data. An active process appears to shape signal waveform as signals spread laterally in the bipolar cell layer. Chemical synaptic coupling between bipolar cells is considered and shown to be inconsistent with the data. It is suggested that local, transient negative feedback from amacrine cells is involved in shaping bipolar cell signals.

Discrete influx events refill depleted Ca2+ stores in a chick retinal neuron

The depletion of ER Ca2+ stores, following the release of Ca2+ during intracellular signalling, triggers the Ca2+ entry across the plasma membrane known as store‐operated calcium entry (SOCE). We show here that brief, local [Ca2+]i increases (motes) in the thin dendrites of cultured retinal amacrine cells derived from chick embryos represent the Ca2+ entry events of SOCE and are initiated by sphingosine‐1‐phosphate (S1P), a sphingolipid with multiple cellular signalling roles. Externally applied S1P elicits motes but not through a G protein‐coupled membrane receptor. The endogenous precursor to S1P, sphingosine, also elicits motes but its action is suppressed by dimethylsphingosine (DMS), an inhibitor of sphingosine phosphorylation. DMS also suppresses motes induced by store depletion and retards the refilling of depleted stores. These effects are reversed by exogenously applied S1P. In these neurons formation of S1P is a step in the SOCE pathway that promotes Ca2+ entry in the form of motes.

Explaining Lateral Interactions in the Retina with the Help of Models

Making models of the nervous system can be an invaluable and often essential step in understanding how it works. Before describing a particular example of modeling it is perhaps worthwhile to inquire a little more deeply into the relationship between modeling and understanding.