Responses of excitatory hippocampal synapses to natural stimulus patterns reveal a decrease in short‐term facilitation and increase in short‐term depression during postnatal development

Abstract

Schaffer collateral excitatory synapses onto CA1 pyramidal cells are subject to significant modulation by short-term plasticity. This presynaptic, history-dependent modulation of neurotransmitter release causes synaptic transmission to be sensitive to the frequency of the input. As a result, temporally irregular input patterns, such as those observed in vivo, produce synaptic responses over a very wide dynamic range that reflect a balance of short-term facilitation and short-term depression. The neonatal period is an important developmental period in the hippocampus, when functional representations of an animal's environment are being established through exploratory behavior. The strength of excitatory synapses and their modulation by short-term plasticity are critical to this process. One form of short-term plasticity, paired-pulse facilitation, has been shown to decrease as juvenile rats mature into young adults. However, little is known about the neonatal modulation of other forms of short-term plasticity, including the responses to temporally complex stimuli. We examined developmental modulation of the short-term dynamics of Schaffer collateral excitatory synapses onto CA1 pyramidal cells in acute hippocampal slices, using both constant frequency stimuli and natural stimulus patterns that were taken from in vivo recording of spike patterns of hippocampal cells. In response to constant frequency stimulation, synapses in slices from young adult rats (P28-P35) showed less short-term depression than did those in slices from juveniles (P12-P18). However, when the natural stimulus pattern (containing a wide mix of frequencies) was used, synapses from young adults instead showed more short-term depression and less short-term facilitation than did juveniles. Comparing the natural stimulus pattern responses with constant frequency stimulation of a similar frequency, we found that the average responses were similar in young adults (both showed modest depression). However, in juveniles, the natural pattern produced robust facilitation while constant frequency stimulation caused a large short-term depression. Our results reveal that there are developmental changes both in individual forms of short-term plasticity and in the relative balance between short-term facilitation and short-term depression that will alter the signal transfer characteristics of these synapses.

Developmental Decrease in Short-Term Facilitation at Schaffer Collateral Synapses in Hippocampus Is mGluR1 Sensitive

“…Using these natural stimulus patterns, our lab has previously investigated developmental differences in short-term plasticity at Schaffer collateral synapses between juveniles and young adults (Dekay et al 2006). We found that the pattern of responses of Schaffer collateral synapses varied over a wide dynamic range in response to these temporally complex stimuli but was very reproducible from trial to trial for synapses at both ages (juveniles and young adults).…”

“…This activity-dependent modulation of neurotransmitter release occurs on time scales of milliseconds to tens of seconds and causes the strength of synaptic transmission to depend on the recent history of use (reviewed in Zucker and Regehr 2002). At Schaffer collateral synapses, several studies have reported a decrease in a simple form of short-term plasticity, paired-pulse facilitation in slices from young adults compared with juveniles (Dekay et al 2006;Foster 1995, 1998b). In addition, our lab has shown a decrease in short-term depression in response to constant high-frequency trains in young adults versus juveniles (Dekay et al 2006).…”

“…At Schaffer collateral synapses, several studies have reported a decrease in a simple form of short-term plasticity, paired-pulse facilitation in slices from young adults compared with juveniles (Dekay et al 2006;Foster 1995, 1998b). In addition, our lab has shown a decrease in short-term depression in response to constant high-frequency trains in young adults versus juveniles (Dekay et al 2006). Changes therefore occur in both the strength and dynamics of Schaffer collateral synapses during early postnatal development.…”

“…Previous studies have shown that synaptic strength varies over a wide dynamic range in response to stimulus patterns taken from in vivo recordings of action potential timing from hippocampal place cells (Dekay et al 2006;Dobrunz and Stevens 1999). These patterns are temporally complex, consisting of bursts of stimuli with short interstimulus intervals separated by long intervals with little or no activity (Fenton and Muller 1998) and have been referred to as natural stimulus patterns to reflect their physiological origin (Dobrunz and Stevens 1999).…”

Distinct roles for Cav2.1–2.3 in activity-dependent synaptic dynamics

“…stage (Dekay et al 2006) and recording temperature (Klyachko and Stevens 2006), which was part of the rationale underlying our decision to use adult mice, recordings at near-physiological temperatures, and stimulus patterns similar to the activity seen in vivo. We note that the relief of prepulse inhibition that underlies the results seen in Scheuber et al (2004) is steeply dependent on the duration of the depolarization, requiring a relatively slow spike waveform (Park and Dunlap 1998); one possible explanation for the discrepancy is that the faster kinetics of spiking at near-physiological temperatures may be unable to recruit this effect, allowing us to more cleanly assess other mechanisms by which each channel subtype contributes to synaptic dynamics.…”