Probability of Transmitter Release at Neocortical Synapses at Different Temperatures

Abstract

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...

Developmental Switch in the Contribution of Presynaptic and Postsynaptic NMDA Receptors to Long-Term Depression

“…We suggest that presynaptic NMDARs may be needed to support high neurotransmitter release probabilities. This idea is consistent with the general observations that the probability of neurotransmitter release is much greater early in development, when presynaptic NMDARs are presumably present, than at later stages of development, when they are more likely to be absent (Bolshakov and Siegelbaum, 1995;Choi and Lovinger, 1997;Reyes and Sakmann, 1999;Silver et al, 2003;Volgushev et al, 2004). A high probability of neurotransmitter release in immature synapses may be needed for terminals to make their initial postsynaptic connections and to maintain neurotransmission when postsynaptic receptors are fewer in number (Rumpel et al, 2004).…”

Physiological Temperatures Reduce the Rate of Vesicle Pool Depletion and Short-Term Depression via an Acceleration of Vesicle Recruitment

“…In contrast, studies in cortical synapses have concluded that p r increases at Ͼ32°C (Hardingham and Larkman, 1998;Volgushev et al, 2004). Synapses in different locations in the brain may thus behave differently to increased temperature.…”

“…At the calyx of Held, shifting temperature to near-physiological values slightly reduces the total Ca 2ϩ charge entry during a single action potential (AP) (Borst and Sakmann, 1998), but corresponding variations of p r with temperature have not been measured. Previous electrophysiological studies examining the effect of temperature on p r at other CNS synapses have led to different results (Allen and Stevens, 1994;Hardingham and Larkman, 1998;Pyott and Rosenmund, 2002;Volgushev et al, 2004) and have not distinguished the effects of temperature on presynaptic Ca 2ϩ entry from downstream effects on vesicle fusion. Recent imaging studies have shown that the kinetics of synaptic vesicle exocytosis and endocytosis is strongly temperature dependent (Yang et al, 2005), underscoring its fundamental importance for synaptic function.…”

FEF inactivation with improved optogenetic methods

“…The maximum temperature increase recorded on any of the thermocouples was considered the "temperature" increase. Guided by reports in the literature, a temperature increase of >4°C was set as the threshold for damage (54)(55)(56)(57), whereas a change of >2°C was set as the threshold for possibly inducing changes in the neuronal firing rate, opening transient receptor potential (TRP) channels, or increasing the probability of neurotransmitter release (89)(90)(91)(92)(93)(94). To be conservative relative to the literature, we sought to keep the temperature within 1°C of baseline after a 1-s test pulse, and eventually elected to use only 300-ms pulses in the actual study.…”