Maturation of Schaffer collateral synapses generates a phenotype of unreliable basal evoked release and very reliable facilitated release

Abstract

Short-term synaptic plasticity undergoes important age-dependent changes that have crucial implications during the development of the nervous system. Paired-pulse facilitation is a form of short-term synaptic plasticity by which the response to the second of two temporally-paired stimuli is larger and more reliable than the response to the first stimulus. In this study, a paired-pulse minimal stimulation technique was used to measure the probability and quantal amplitude of synaptic release at hippocampal synapses from 12–16-day-old (young) and 7–9-week-old (adult) rats. In order to assess the contribution of temperature-dependent processes, we carried out experiments at both room temperature and at near physiological temperature. We report here that neither temperature nor maturation affected the low basal evoked release probability and quantal amplitude of release. However, the warmer temperature revealed a unique developmental increase in facilitated evoked release probability and quantal amplitude of release. As a result, although both basal evoked release and facilitated release are rather unreliable in synapses from young animals, the maturation process at near physiological temperature generates a phenotype with unreliable basal evoked release and highly reliable facilitated release.

Changes in long-range connectivity and neuronal reorganization in partial cortical deafferentation model of epileptogenesis

“…This assumption is indirectly supported by the fact that the amplitude of somatic EPSPs is increased in the undercut cortex (Avramescu and Timofeev, 2008) as some, although not major, attenuation is caused by the spine neck that reduces the amplitude of somatic EPSPs (Palmer and Stuart, 2009), implying that an increase in the amplitude of successful EPSPs might be caused by synapses formed on dendritic shafts. A formation of new synapses (before maturation) is characterized by high failure rates (Schiess et al, 2010), which was also observed in our previous study (Avramescu and Timofeev, 2008). Further quantitative electron microscope studies are needed to confirm an increase in the number of synapses on dendritic shafts.…”

Klotho regulates CA1 hippocampal synaptic plasticity

“…PPF change without a concurrent initial release probability change is reported and when reported, the underlying mechanism remains pre-synaptic (e.g. (Kokaia et al, 1998, Sippy et al, 2003, Sun and Dobrunz, 2006, Speed and Dobrunz, 2009, Schiess et al, 2010, Walters et al, 2014). Our data are consistent with the previous study that measured 7 week KO LTP and found no change with a similar stimulation pattern, rather only when neurons were lightly stimulated by a single theta burst (Park et al, 2013).…”

Presynaptic residual calcium and synaptic facilitation at hippocampal synapses of mice with altered expression of SNAP-25

“…While our ΔF/F 0 measurement does not directly assess the Ca 2+ that is responsible for vesicular release, it is representative of the saturation of the mechanisms that determine the timecourse of presynaptic [Ca 2+ ] res (Scullin and Partridge, 2010). Furthermore, we and others have shown [Ca 2+ ] res to be a critical determinant of the facilitation of the post-synaptic response (Schiess et al, 2010; Wu and Saggau, 1994; Zucker and Regehr, 2002). When the same analysis was performed on the data derived from slices of Tkneo, HET, and WT mice, we found that the ratio of ∫ΔF/F 0 resulting from paired-pulses to that from a single pulse was larger than two for all three genotypes and significantly greater for Tkneo than for either HET or WT mice (Figure 4E).…”

“…Because our modeling studies indicated an influence of Snap25 genotype on [Ca 2+ ] res clearance, we measured the kinetics of the ΔF/F 0 transients that accompanied PPF (Schiess et al, 2006; Schiess et al, 2010; Scullin et al, 2010; Wu and Saggau, 1994). As expected from our previous measurements in rats (Schiess et al, 2006), we found a linear relationship between the transient ΔF/F 0 response of the first (F1) and that of the second (F2) of paired stimuli with a greater than unity slope.…”

“…Since the ratio of SNAP-25a to SNAP-25b in adult Tkneo mice is similar to that of P4 - P7 mice, we investigated two important mechanisms of [Ca 2+ ] res regulation that are known to change between P2 - P6 and adult (Scullin et al, 2010). First, we assessed the contribution of the SERCA pump to the uptake of presynaptic [Ca 2+ ] into the ER (Schiess et al, 2010) by using thapsigargin to block SERCA pump activity (Verkhratsky, 2005). As expected, application of 3 μM thapsigargin slowed [Ca 2+ ] res clearance as indicated by a significantly increased ∫νΔF/F 0 in thapsigargin to that in ACSF following a single pulse in the WT and, importantly, it led to a similar increase in Tkneo mice (Students t-test, P = 0.32, Figure 6A).…”