Volgushev, Maxim, Igor Kudryashov, Marina Chistiakova, Mikhail Mukovski, Johannes Niesmann, and Ulf T. Eysel. Probability of transmitter release at neocortical synapses at different temperatures. J Neurophysiol 92: 212-220, 2004. First published March 3, 2004 10.1152/jn.01166.2003. The probability of transmitter release at synaptic terminals is one of the key characteristics of communication between nerve cells because it determines both the strength and dynamic properties of synaptic connections. To assess the distribution of the release probabilities at excitatory synapses on supragranular pyramidal cells in rat visual cortex, we have used the MK-801, a blocker of the open N-methyl-D-aspartate (NMDA) receptor-gated channels. With this method, the release probability can be calculated from the time course of the blockade of NMDA-receptor mediated postsynaptic currents in the presence of MK-801. At temperatures Ͼ32°C, the distribution of release probabilities covered the range from 0.05 to 0.43 [mean: 0.171 Ϯ 0.012 (SE), n ϭ 65], being skewed toward low values. When estimated at room temperature (22-25°C), the release probabilities were significantly lower (mean: 0.123 Ϯ 0.009, n ϭ 54), and almost the whole distribution was restricted to values Ͻ0.2. Furthermore, warming from room temperature to Ͼ32°C led to a pronounced overshooting increase of the release probability. Taken together, the results of the present study show that release probabilities at synapses formed onto layer 2/3 pyramidal cells in the visual cortex vary significantly, but values Ͼ0.3 are rare and the results obtained either at room or variable temperature differ significantly from those made under conditions of constant temperature in the physiological range. I N T R O D U C T I O NKnowledge about the probability of transmitter release and its changes at neocortical synapses is a necessary step toward understanding information processing by neural networks in sensory areas. Data available for the synaptic connections in the neocortex show that the release probability of synapses at neurons of similar morphological type are more uniform than the release probability of synapses at cells of different morphology (see Thomson and Deuchars 1994 for review;Markram et al. 1998;Reyes et al. 1998;Tsodyks and Markram 1997). These estimates of the release probability at neocortical synapses, as well as more numerous data on synaptic transmission in the hippocampus (e.g., Allen and Stevens 1994;Bolshakov and Siegelbaum 1995;Stricker et al. 1996; Voronin et al. 1992), were obtained by use of statistical analysis of the amplitude fluctuations of the postsynaptic responses. Another method, which allows estimation of the release probability, is based on the irreversible block of the N-methyl-D-aspartate (NMDA) receptor-gated channels by MK-801 (Huettner and Bean 1988). Because the MK-801 blocks only open channels, the rate of the blockade of the NMDA receptor-mediated synaptic responses depends on the release probability. This method has been successfully...

Slices from rat hippocampus were incubated with the caspase-3 inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp fluoromethylketone (Z-DEVD-FMK) or with the inactive peptide N-benzyloxycarbonyl-Phe-Ala fluoromethylketone (Z-Phe-Ala-FMK) for 30 min. The peptides changed neither input-output curves nor paired-pulse effects at 70-msec interpulse intervals, nor amplitudes of pop spikes in the CA1 region 1.0-6.9 hr after the incubation. Slices taken 1.0-1.4 hr after Z-DEVD-FMK or inactive peptide treatment demonstrated similar long-term potentiation (LTP) curves; however, LTP was suppressed significantly (P<0.001) 1.5-3.4 hr after Z-DEVD-FMK treatment when compared to the corresponding inactive peptide group. LTP magnitude correlated with time after Z-DEVD-FMK (r= -0.74; P<0.02) but did not depend on time after the inactive peptide treatment. After 3.5 hr, LTP was blocked completely. Z-DEVD-FMK did not have a significant effect on presynaptic function. The results are the first evidence that inhibition of caspase-3 significantly decreases or fully blocks LTP in the CA1 region and suggest that caspase-3 is essential for LTP. Candidate caspase-3 substrates that may be cleaved for LTP induction and maintenance are discussed.

Electrophysiological measures of the functional activity of neurons in field CA1 in conditions of paired-pulse stimulation of Schäffer collaterals were performed in relation to the involvement of caspase-3 in mediating neuroplasticity; the relationship between functional activity and caspase-3 activity in hippocampal slices from Wistar rats was addressed. Enzyme activity was assessed in each individual slice at the end of the electrophysiological experiment. The results obtained here showed that the highest level of enzyme activity was seen when the efficiency of interneuronal interactions decreased. Nerve cell excitability showed no changes; interactions increasing synaptic efficiency, particularly in paired-pulse stimulation, produced normal response amplitudes. Further deterioration of the functional state of slices and impairments in spike generation were accompanied by increases in caspase-3 activity to the normal level. Increases in the activity of another proteinase, cathepsin B, were generally seen in any deviation from normal functioning, though there was no correlation with any of the electrophysiological parameters. It is suggested that high caspase-3 activity in slices is linked with neuroplastic processes in synapses and has no direct relationship to nerve cell apoptosis.

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