Abstract
During development, hippocampal CA3 network generates recurrent population bursts, so-called Giant Depolarizing Potentials (GDPs). GDPs are characterized by synchronous depolarization and firing of CA3 pyramidal cells followed by afterhyperpolarization (GDP-AHP). Here, we explored the properties of GDP-AHP in CA3 pyramidal cells using gramicidin perforated patch clamp recordings from neonatal rat hippocampal slices. We found that GDP-AHP occurs independently of whether CA3 pyramidal cells fire action potentials (APs) or remain silent during GDPs. However, the amplitude of GDP-AHP increased with the number of APs the cells fired during GDPs. The reversal potential of the GDP-AHP was close to the potassium equilibrium potential. During voltage-clamp recordings, current-voltage relationships of the postsynaptic currents activated during GDP-AHP were characterized by reversal near the potassium equilibrium potential and inward rectification, similar to the responses evoked by the GABA(B) receptor agonists. Finally, the GABA(B) receptor antagonist CGP55845 strongly reduced GDP-AHP and prolonged GDPs, eventually transforming them to the interictal and ictal-like discharges. Together, our findings suggest that the GDP-AHP involves two mechanisms: (i) postsynaptic GABA(B) receptor activated potassium currents, which are activated independently on whether the cell fires or not during GDPs; and (ii) activity-dependent, likely calcium activated potassium currents, whose contribution to the GDP-AHP is dependent on the amount of firing during GDPs. We propose that these two complementary inhibitory postsynaptic mechanisms cooperate in the termination of GDP.
Highlights
Giant Depolarizing Potentials (GDPs) were observed as recurrent polysynaptic events associated with multiple unit activity (MUA) bursts and local field potential (LFP) events during extracellular recordings occurring at 0.06 ± 0.01 Hz in all hippocampal slices of P4–8 rats (n = 23 cells; Figure 1)
The principal finding of the present study is that the GDP-AHP in neonatal CA3 pyramidal cells is generated through the cooperation of postsynaptic GABA(B) receptor activated potassium currents (Component 1) and spike-dependent, likely calcium activated, potassium currents (Component 2)
While previous studies mainly focused on the mechanisms underlying synchronous depolarization and firing of neurons during GDPs in the neonatal hippocampus, relatively few addressed the mechanisms underlying AHP following GDPs
Summary
Giant Depolarizing Potentials (GDPs) are a ubiquitous network activity pattern observed both in neonatal rodent and fetal primate hippocampal slices and in the isolated intact rat hippocampus (Ben-Ari et al, 1989; Khalilov et al, 1997; Leinekugel et al, 1998; Khazipov et al, 2001; for reviews, Ben-Ari et al, 2007; Blankenship and Feller, 2010; Cherubini et al, 2011). While neonatal CA3 pyramidal cells and neocortical neurons lack late GABA(B) receptor mediated component during monosynaptically evoked GABAergic responses, they start to respond to the GABA(B) receptor agonist baclofen as early as at the postnatal day P3 (Luhmann and Prince, 1991; Fukuda et al, 1993; Gaiarsa et al, 1995; Caillard et al, 1998; Nurse and Lacaille, 1999; Verheugen et al, 1999) This raises a possibility that postsynaptic GABA(B) receptors could be activated by massive release of GABA during GDPs. blockade of GABA(B) receptors was shown to prolong GDPs and transform them to the interictal- and ictal-like discharges (McLean et al, 1996). Analysis of the effect of the GABA(B) receptor antagonists on GDPs has been only performed using potassium channel blockers in the pipette solution (McLean et al, 1996) and the contribution of the postsynaptic GABA(B) receptors to the GDP-AHP remains elusive
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