Search

Neuronal timing with millisecond precision is critical for many brain functions such as sensory perception, learning and memory formation. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). For instance, paired-pulse facilitation or presynaptic long-term potentiation are associated with reductions in the synaptic delay, whereas paired-pulse depression or presynaptic long-term depression are associated with an increased synaptic delay. Parallelly, the AP broadening that results from the inactivation of voltage gated potassium (Kv) channels responsible for the repolarization phase of the AP delays the synaptic response, and the inactivation of sodium (Nav) channels by voltage reduces the synaptic latency. However, whether synaptic delay is modulated during depolarization-induced analogue–digital facilitation (d-ADF), a form of context-dependent synaptic facilitation induced by prolonged depolarization of the presynaptic neuron and mediated by the voltage-inactivation of presynaptic Kv1 channels, remains unclear. We show here that despite Pr being elevated during d-ADF at pyramidal L5-L5 cell synapses, the synaptic delay is surprisingly unchanged. This finding suggests that both Pr- and AP-dependent changes in synaptic delay compensate for each other during d-ADF. We conclude that, in contrast to other short- or long-term modulations of presynaptic release, synaptic timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay. [ABSTRACT FROM AUTHOR]

Neuronal timing with millisecond precision is critical for many brain functions such as sensory perception, learning and memory formation. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). For instance, paired-pulse facilitation or presynaptic long-term potentiation are associated with reductions in the synaptic delay, whereas paired-pulse depression or presynaptic long-term depression are associated with an increased synaptic delay. Parallelly, the AP broadening that results from the inactivation of voltage gated potassium (Kv) channels responsible for the repolarization phase of the AP delays the synaptic response, and the inactivation of sodium (Nav) channels by voltage reduces the synaptic latency. However, whether synaptic delay is modulated during depolarization-induced analogue–digital facilitation (d-ADF), a form of context-dependent synaptic facilitation induced by prolonged depolarization of the presynaptic neuron and mediated by the voltage-inactivation of presynaptic Kv1 channels, remains unclear. We show here that despite Pr being elevated during d-ADF at pyramidal L5-L5 cell synapses, the synaptic delay is surprisingly unchanged. This finding suggests that both Pr- and AP-dependent changes in synaptic delay compensate for each other during d-ADF. We conclude that, in contrast to other short- or long-term modulations of presynaptic release, synaptic timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

Highlights: [•] Low probability of secretion is accompanied by long synaptic delays at infant rats. [•] Quantal release is significantly asynchronous at the synapses of infant rats. [•] Ryanodine receptor blockade does not eliminate the asynchronous release in newborn. [ABSTRACT FROM AUTHOR]

Abstract: Quantal analysis of synaptic transmission is an important tool for understanding the mechanisms of synaptic plasticity and synaptic regulation. Although several custom-made and commercial algorithms have been created for the analysis of spontaneous synaptic activity, software for the analysis of action potential evoked release remains very limited. The present paper describes a user-friendly software package QUANTAN which has been created to analyze electrical recordings of postsynaptic responses. The program package is written using Borland C++ under Windows platform. QUANTAN employs and compares several algorithms to extract the average quantal content of synaptic responses, including direct quantal counts, the analysis of synaptic amplitudes, and the analysis of integrated current traces. The integration of several methods in one user-friendly program package makes quantal analysis of action potential evoked release more reliable and accurate. To evaluate the variability in quantal content, QUANTAN performs deconvolution of the distributions of amplitudes or areas of synaptic responses employing a ridge regression method. Other capabilities of QUANTAN include the analysis of the time-course and stationarity of quantal release. In summary, QUANTAN uses digital records of synaptic responses as an input and computes the distribution of quantal content and synaptic parameters. QUANTAN is freely available to other scholars over the internet. [Copyright &y& Elsevier]