Effects of μ-Opioid Receptor Modulation on GABA_B Receptor Synaptic Function in Hippocampal CA1

Abstract

McQuiston AR. Effects of -opioid receptor modulation on GABA B receptor synaptic function in hippocampal CA1. J Neurophysiol 97: 2301-2311, 2007. First published January 10, 2007 doi:10.1152/jn.01179.2006. Activation of -opioid receptors (MORs) alters information coding, synaptic plasticity, and spatial memory in hippocampal CA1. In CA1, MORs act by inhibiting GABA release onto both GABA A and GABA B receptors exclusively. MOR activation can facilitate excitatory inputs in CA1 dendritic layers by inhibiting synaptic activation of GABA A receptors. In this study, we use voltage-sensitive dye imaging to show that MOR activation by the MOR agonist DAMGO suppressed GABA B inhibitory postsynaptic potentials in all layers of CA1. When stimulating excitatory input in stratum oriens (SO), stratum radiatum (SR), or stratum lacunosummoleculare (SLM) with five pulses at 20 Hz in the presence of bicuculline (50 M), DAMGO (1 M) was most effective at increasing the amplitude of the last excitatory event. This effect was reversed by the MOR antagonist CTOP (1 M) and occluded by the GABA B receptor agonist CGP 55845 (10 M). DAMGO was less effective at increasing the amplitude of later excitatory events compared with the effect of CGP 55845. DAMGO was relatively ineffective at increasing the amplitude of excitatory inputs in SLM but had significantly greater effects on excitatory events as they propagated to stratum pyramidale (SP). When stimulating in SR, DAMGO was least effective at increasing excitatory amplitudes in SLM and most effective in SP and SO. Finally, DAMGO was equally effective at increasing excitatory activity amplitudes in all layers of CA1 after stimulating in SO. Therefore MOR suppresses GABA B synaptic hyperpolarizations in all layers of CA1 and most effectively facilitates excitatory activity in CA1 output layers.

Layer selective presynaptic modulation of excitatory inputs to hippocampal cornu Ammon 1 by μ-opioid receptor activation

“…Previous studies have suggested that MOR activation can influence excitatory activity in all layers of hippocampal CA1 (McQuiston and Saggau, 2003;McQuiston, 2007). However, the relative effectiveness of MOR activation in the discrete layers of CA1 is not fully understood.…”

“…However, a physiological study reported that less than half of interneurons projecting to the proximal apical dendrites in SR were hyperpolarized by MOR activation (Svoboda et al, 1999). Yet other physiological studies have shown that MOR activation can significantly increase the amplitude of excitatory inputs in SR (McQuiston and Saggau, 2003;McQuiston, 2007). To examine the effect of MOR activity on excitatory inputs in SR, SR was isolated from SP by a razor cut between SP and SR (Fig.…”

“…More recent physiological studies have shown that MOR activation significantly affected the dendritic layers of CA1 by increasing the size of excitatory inputs in CA1 and augmenting excitatory activity that propagated between layers of CA1 (McQuiston and Saggau, 2003;McQuiston, 2007). The simplest explanation for these observations was that MORs were found in sufficient concentrations in CA1 dendritic layers to be as effective at modulating excitatory activity in the dendritic layers of CA1 as they were at modulating excitatory activity in the soma of pyramidal cells.…”

“…The simplest explanation for these observations was that MORs were found in sufficient concentrations in CA1 dendritic layers to be as effective at modulating excitatory activity in the dendritic layers of CA1 as they were at modulating excitatory activity in the soma of pyramidal cells. However, these studies were done in intact slices in which inhibition at a particular site in a CA1 pyramidal cell may influence a more distant compartment of the same cell through the cable properties of its dendrites (McQuiston, 2007). Thus, an effect of MOR activation on inhibition in a more proximal layer of CA1 could possibly influence a more distal dendritic layer.…”

Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

“…At 4 weeks following cell injection, rat brain slices were prepared as described previously (McQuiston, 2007). Briefly, the rats were deeply anesthetized with ketamine (200 mg/kg) and xylazine (20 mg/kg), transcardially perfused with ice-cold buffer (consisting of in mM: sucrose 230, KCl 2.5, CaCl 1, MgCl 2 4, NaHPO 4 1, NaHCO 3 25, and glucose 25) and sacrificed by decapitation.…”