Dopamine Modulates Spike Timing-Dependent Plasticity and Action Potential Properties in CA1 Pyramidal Neurons of Acute Rat Hippocampal Slices

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.

Dopamine regulates intrinsic excitability thereby gating successful induction of spike timing-dependent plasticity in CA1 of the hippocampus

“…However, even with a given species and age, and employing a similar STDP protocol, different learning rules have been described (compare Wittenberg and Wang, 2006; Campanac and Debanne, 2008). In the light of recent studies indicating a regulation of STDP either by DA in the striatum (Pawlak and Kerr, 2008; Pawlak et al, 2010), by ISO and ACh in the neocortex (Seol et al, 2007), or by DA in dissociated hippocampal cultures (Zhang et al, 2009), and given our own results of DA-dependent modulation of STDP in CA1 of hippocampal slices (Edelmann and Lessmann, 2011), we hypothesize that the availability of specific neuromodulators critically determine the efficacy of STDP induction in the hippocampus. Thus, the previous discordant results (see above and Table 1) for t-LTP in CA1 might be explained on the basis of differential availability of endogenous neuromodulators in hippocampal slices used in these studies.…”

“…Interestingly, inhibition of D1 receptors in ACSF control slices inhibited t-LTP and also prolonged AP rise times (Figure 2). Overall, these results suggest that ambient levels of endogenous DA in hippocampal slices critically determine the efficiency of STDP induction in CA1, potentially by modulating properties of backpropagating APs during STDP induction (compare Edelmann and Lessmann, 2011). …”

“…To investigate STDP in the CA1 region, we applied whole cell patch clamp recordings from pyramidal neurons of acute hippocampal slices of rats and mice (for details, see Edelmann and Lessmann, 2011). Briefly, STDP was induced by extracellular stimulation of the Schaffer collaterals with a STDP paradigm consisting of one presynaptic and (mostly) one postsynaptic AP stimulation with a time delay of +5 to +10 ms.…”

“…Whereas these neuromodulators are known since a while to affect conventional LTP and LTD (for a recent review see e.g., Lisman et al, 2011), their cellular and molecular mechanisms of action in regulating timing dependent (t-)LTP and t-LTD , respectively, has just started to be investigated. In comparison to STDP in neocortex and striatum, the determinants of STDP in CA1 of hippocampal slices are less clear (see e.g., Buchanan and Mellor, 2010; Edelmann and Lessmann, 2011). In this focused review we will discuss the role of neuromodulators (especially DA) in the hippocampus for establishing STDP in the CA1 subfield of the hippocampus.…”

Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats

“…Because the timing between pre-and postsynaptic firing specifies synaptic change, tLTP has become an attractive mechanism to model naturally occurring plasticity, particularly in learning-induced changes in cortical cells. The threshold, magnitude, timing window, and gating of tLTP is influenced by catecholaminergic inputs in the cortex and the hippocampus (Lin et al 2003;Seol et al 2007;Zhang et al 2009;Xu and Yao 2010;Edelmann and Lessmann 2012). In the present study, we examined the role of prefrontal cortical b2-AR in tLTP with timing-dependent stimulation of pre-and postsynaptic activity.…”