Presynaptic μ and δ Opioid Receptor Modulation of GABA_AIPSCs in the Rat Globus PallidusIn Vitro

Abstract

The role of enkephalin and the opioid receptors in modulating GABA release within the rat globus pallidus (GP) was investigated using whole-cell patch recordings made from visually identified neurons. Two major GP neuronal subtypes were classified on the basis of intrinsic membrane properties, action potential characteristics, the presence of the anomalous inward rectifier (Ih), and anode break depolarizations. The mu opioid receptor agonist [D-Ala2-N-Me-Phe4-Glycol5]-enkephalin (DAMGO) (1 microM) reduced GABAA receptor-mediated IPSCs evoked by stimulation within the striatum. DAMGO also increased paired-pulse facilitation, indicative of presynaptic mu opioid receptor modulation of striatopallidal input. In contrast, the delta opioid agonist D-Pen-[D-Pen2, 5]-enkephalin (DPDPE) (1 microM) was without effect. IPSCs evoked by stimulation within the GP were depressed by application of [methionine 5']-enkephalin (met-enkephalin) (30 microM). Met-enkephalin also reduced the frequency, but not the amplitude, of miniature IPSCs (mIPSCs) and increased paired-pulse facilitation of evoked IPSCs, indicative of a presynaptic action. Both DAMGO and DPDPE reduced evoked IPSCs and the frequency, but not amplitude, of mIPSCs. However, spontaneous action potential-driven IPSCs were reduced in frequency by met-enkephalin and DAMGO, whereas DPDPE was without effect. Overall, these results indicate that presynaptic mu opioid receptors are located on striatopallidal terminals and pallidopallidal terminals of spontaneously firing GP neurons, whereas presynaptic delta opioid receptors are preferentially located on terminals of quiescent GP cells. Enkephalin, acting at both of these receptor subtypes, serves to reduce GABA release in the GP and may therefore act as an adaptive mechanism, maintaining the inhibitory function of the GP in basal ganglia circuitry.

Distinct Functional Roles of the Metabotropic Glutamate Receptors 1 and 5 in the Rat Globus Pallidus

“…A consensus from many studies is that type A, also referred to as type II neurons (Nambu and Llinas, 1994;Stanford and Cooper, 1999;Shindou et al, 2001), are the predominant electrophysiological phenotype in the rodent GP (Cooper and Stanford, 2000). Here, we report that activation of mGluR1, but not mGluR5, depolarizes type II GP neurons.…”

“…The first property was a sag in membrane potential during a hyperpolarizing current injection in current clamp that corresponds to a time-and voltage-dependent inward current I h . The second property was the presence of anodal breaks after a hyperpolarizing step, suggesting the presence of a low-threshold-activated Ca 2ϩ current I t (Nambu and Llinas, 1994;Stanford and Cooper, 1999;Cooper and Stanford, 2000). These neurons were also characterized by a high input resistance (712 Ϯ 150 M⍀) and spontaneous activity at rest (Fig.…”

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

“…These parameters correspond to the level of striatal input to GPe and interpallidal inhibition, respectively. Note that experimental results show an increase in striatal inhibition to GPe (e.g., Albin et al, 1989) and a decrease in intrapallidal inhibition (Stanford et al, 1999;Ogura et al, 2000) in parkinsonian conditions. By a "normal state", we mean that the parameters are chosen so that the STN/GPe network produces the irregular pattern shown in left panels of Fig.…”

Firing rate and pattern heterogeneity in the globus pallidus arise from a single neuronal population

“…Early studies indicated that there may be as many as three electrophysiologically distinct types of neurons in the rodent GPe (Nambu and Llinas 1994, 1997, Stanford and Cooper 1999Cooper and Stanford 2000). Later authors have suggested that there is one predominant subtype that is autonomously active and fires in a tonic fashion (Chan et al 2004;Günay et al 2008;Deister et al 2009).…”

“…The globus pallidus (GPe) consists of autonomously active GABAergic neurons (Chan et al 2004) that share common inputs and connect to each other via local axon collaterals (Kita and Kitai 1994;Sadek et al 2007). However, the GPe does not display synchronous rhythms and there are no clear correlations between its neurons in healthy mammals (Bar-Gad et al 2003;Nini et al 1995;Raz et al 2000;Mallet et al 2008) or even among neurons in slices (Stanford 2003). In contrast, strong correlations between GPe neurons emerge in Parkinson's disease patients and MPTP-treated primates (Levy et al 2002;Nini et al 1995;Raz et al 2000).…”