Abstract
Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10–20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons.
Highlights
Long-term potentiation (LTP) and long-term depression (LTD) are considered as neuronal substrates for learning and memory
In an attempt to establish a Spike timing-dependent plasticity (STDP) paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction
Significant timingdependent potentiation (t-LTP) for short positive pairings could only be achieved in case of ACSF preparation [Figure 2D, ANOVA F (6,82) = 13.04; p < 0.0001, post hoc Tukey test: *p < 0.05: Δt = +15 ms vs. Δt = +30 ms, ***p < 0.0001: Δt = +15 ms vs. CTRL and Δt = −15 ms, respectively], while sucrose prepared slices failed to reveal a clear learning rule with the STDP paradigms used in our study (Figure 2D: p > 0.05)
Summary
Long-term potentiation (LTP) and long-term depression (LTD) are considered as neuronal substrates for learning and memory. It is well established that repetitive pairing of an EPSP and a single action potential induces STDP in dissociated cultures of hippocampal neurons (e.g., Bi and Poo, 1998; Gerkin et al, 2007), in CA1 pyramidal cells of organotypic slices (Debanne et al, 1994, 1996), or in CA1 of acute hippocampal slices of very young animals (Meredith et al, 2003, P9–14 mice). While Nishiyama et al (2000) and Campanac and Debanne (2008) reported t-LTP after repetitive pairing of an EPSP with a single action potential in CA1 of acute hippocampal slices from P26–P33 or P15–P20 rats, respectively, neither Pike et al (1999, young adult rats), Wittenberg and Wang (2006, P14– 28 rats), Remy and Spruston (2007, 3- to 5-weeks-old rats), nor Carlisle et al (2008, 4–12 month old mice) could show t-LTP with single spike pairing conditions in the hippocampal CA1 region
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