Electrophysiological interactions of enkephalins with neuronal circuitry in the rat hippocampus. II. Effects on interneuron excitability

Lee, H.K.; Dunwiddie, Thomas V.; Hoffer, Barry J.

doi:10.1016/0006-8993(80)90802-1

Cited by 126 publications

(33 citation statements)

References 22 publications

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“…The finding that opioids hyperpolarize local intemeurons is consistent with results in the hippocampus and olfactory bulb (Nicoll et al, 1980;Madison and Nicoll, 1988); the finding that they do so by increasing the membrane potassium conductance is consistent with results in many mammalian neurons (reviewed by North, 1992). It has been generally inferred that hyperpolarization of inhibitory intemeurons accounts for the excitation of hippocampal pyramidal cells (Nicoll et al, 1977;Zieglgansberger et al, 1979;Lee et al, 1980), and consistent with this is the finding that GABA,-mediated synaptic potentials recorded from pyramidal cells are reduced by opioids (Siggins and Zieglgansberger, 198 1). Four results of the present work converge on the conclusion that in the case of the VTA, the dopamine-containing output neurons are excited through disinhibition.…”

Section: Damgosupporting

confidence: 71%

Opioids excite dopamine neurons by hyperpolarization of local interneurons

1992

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Increased activity of dopamine-containing neurons in the ventral tegmental area is necessary for the reinforcing effects of opioids and other abused drugs. Intracellular recordings from these cells in slices of rat brain in vitro showed that opioids do not affect the principal (dopamine-containing) neurons but hyperpolarize secondary (GABA- containing) interneurons. Experiments with agonists and antagonists selective for opioid receptor subtypes indicated that the hyperpolarization of secondary cells involved the mu-receptor. Most principal cells showed spontaneous bicuculline-sensitive synaptic potentials when the extracellular potassium concentration was increased from 2.5 to 6.5 or 10.5 mM; these were prevented by TTX and assumed to result from action potentials arising in slightly depolarized local interneurons. The frequency of these synaptic potentials, but not their amplitudes, was reduced by opioids selective for mu-receptors. It is concluded that hyperpolarization of the interneurons by opioids reduces the spontaneous GABA-mediated synaptic input to the dopamine cells. In vivo, this would lead to excitation of the dopamine cells by disinhibition, which would be expected to contribute to the positive reinforcement seen with mu-receptor agonists such as morphine and heroin.

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Section: Damgosupporting

confidence: 71%

Opioids excite dopamine neurons by hyperpolarization of local interneurons

1992

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“…More specifically, MOR-induced hyperpolarizations were more frequently observed in stratum oriens (SO) interneurons that targeted the pyramidal cell body layer than in interneurons projecting to their dendrites (Svoboda et al 1999). These authors interpreted this observation to be consistent with previous extracellular electrophysiological studies that described an MOR-induced increase in the excitability of pyramidal cells' somata, with no concomitant effect on excitatory inputs to their dendrites (Corrigall and Linseman 1980;Dingledine 1981;Haas and Ryall 1980;Lee et al 1980;Lynch et al 1981;Martinez et al 1979;Zieglgansberger et al 1979). Furthermore, discrete application of opioid agonists to the cell body region of CA1 produced a larger and more consistent increase in pyramidal cell body excitability, than application to the apical dendrites (Dingledine 1981;Robinson and Deadwyler 1981).…”

Section: Introductionsupporting

confidence: 70%

Mu-opioid Receptors Facilitate the Propagation of Excitatory Activity in Rat Hippocampal Area CA1 by Disinhibition of all Anatomical Layers

McQuiston

Saggau

2003

Journal of Neurophysiology

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Hippocampal μ-opioid receptors (MORs) have been implicated in memory formation associated with opiate drug abuse. MORs modulate hippocampal synaptic plasticity acutely, when chronically activated, and during drug withdrawal. At the network level, MORs increase excitability in area CA1 by disinhibiting pyramidal cells. The precise inhibitory interneuron subtypes affected by MOR activation are unknown; however, not all subtypes are inhibited, and specific interneuron subtypes have been shown to preferentially express MORs. Here we investigate, using voltage-sensitive dye imaging in brain slices, the effect of MOR activation on the patterns of inhibition and on the propagation of excitatory activity in rat hippocampal CA1. MOR activation augments excitatory activity evoked by stimulating inputs in stratum oriens [i.e., Schaffer collateral and commissural pathway (SCC) and antidromic], stratum radiatum (i.e., SCC), and stratum lacunosum-moleculare (SLM; i.e., perforant path and thalamus). The augmented excitatory activity is further facilitated as it propagates through the CA1 network. This was observed as a proportionately larger increase in amplitudes of excitatory activity at sites distal from where the activity was evoked. This facilitation was observed for excitatory activity propagating from all three stimulation sites. The augmentation and facilitation were prevented by GABAA receptor antagonists (bicuculline, 30 μM), but not by GABAB receptor antagonists (CGP 55845, 10 μM). Furthermore, MOR activation inhibited IPSPs in all layers of area CA1. These findings suggest that MOR-induced suppression of GABA release onto GABAA receptors augments all inputs to CA1 pyramidal cells and facilitates the propagation of excitatory activity through the network of area CA1.

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“…Increased dynorphin levels, as seen in the LI-IGF-I / mice, could therefore reflect a low synaptic activity at the mossy fibre-CA3 pyramidal neurone synapse, not requiring release of inhibitory dynorphin. Enkephalin has predominantly inhibitory effects in the hippocampus, mainly acting on inhibitory gamma-aminobutyric acid (GABA) interneurones (Segal 1977, Lee et al 1980, thus causing disinhibition. Increase in enkephalin peptide together with decreased transcript levels in the granule cell-mossy fibre system could therefore lead to attenuated facilitatory mechanisms in the LI-IGF-I / mice.…”

Section: Discussionmentioning

confidence: 99%

Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice

Svensson¹,

Diez²,

Engel³

et al. 2006

Journal of Endocrinology

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IGF-I is a neuroprotective hormone, and neurodegenerative disorders, including Alzheimer's disease, have been associated with decreased serum IGF-I concentration. In this study, IGF-I production was inactivated in the liver of adult mice (LI-IGF-I / ), resulting in an approximately 80-85% reduction of circulating IGF-I concentrations. In young (6-month-old) mice there was no difference between the LI-IGF-I / and the control mice in spatial learning and memory as measured using the Morris water maze test. In old (aged 15 and 18 months) LI-IGF-I / mice, however, the acquisition of the spatial task was slower than in the controls. Furthermore, impaired spatial working as well as reference memory was observed in the old LI-IGF / mice. Histochemical analyses revealed an increase in dynorphin and enkephalin immunoreactivities but decreased mRNA levels in the hippocampus of old LI-IGF-I / mice. These mice also displayed astrocytosis and increased metabotropic glutamate receptor 7a-immunoreactivity. These neurochemical disturbances suggest synaptic dysfunction and early neurodegeneration in old LI-IGF-I / mice. The decline in serum IGF-I with increasing age may therefore be important for the age-related decline in memory function.

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Electrophysiological interactions of enkephalins with neuronal circuitry in the rat hippocampus. II. Effects on interneuron excitability

Cited by 126 publications

References 22 publications

Opioids excite dopamine neurons by hyperpolarization of local interneurons

Opioids excite dopamine neurons by hyperpolarization of local interneurons

Mu-opioid Receptors Facilitate the Propagation of Excitatory Activity in Rat Hippocampal Area CA1 by Disinhibition of all Anatomical Layers

Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice

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