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Simultaneous release of glutamate and acetylcholine from single magnocellular "cholinergic" basal forebrain neurons

Allen, TGJ; Abogadie, FC; Brown, DA; (2006) Simultaneous release of glutamate and acetylcholine from single magnocellular "cholinergic" basal forebrain neurons. J NEUROSCI , 26 (5) 1588 - 1595. 10.1523/JNEUROSCI.3979-05.2006. Green open access

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Abstract

Basal forebrain (BF) neurons provide the principal cholinergic drive to the hippocampus and cortex. Their degeneration is associated with the cognitive defects of Alzheimer's disease. Immunohistochemical studies suggest that some of these neurons contain glutamate, so might also release it. To test this, we made microisland cultures of single BF neurons from 12- to 14-d-old rats. Over 1-8 weeks in culture, neuronal processes made autaptic connections onto the neuron. In 34 of 36 cells tested, a somatically generated action potential was followed by a short-latency EPSC that was blocked by 1 mM kynurenic acid, showing that they released glutamate. To test whether the same neuron also released acetylcholine, we placed a voltage-clamped rat myoball expressing nicotinic receptors in contact with a neurite. In six of six neurons tested, the glutamatergic EPSC was accompanied by a nicotinic (hexamethonium-sensitive) myoball current. Stimulation of the M-2-muscarinic presynaptic receptors ( characterized using tripitramine and pirenzepine) produced a parallel inhibition of autaptic glutamatergic and myoball nicotinic responses; metabotropic glutamate receptor stimulation produced similar but less consistent and weaker effects. Atropine enhanced the glutamatergic EPSCs during repetitive stimulation by 25 +/- 6%; the anti-cholinesterase neostigmine reduced the train EPSCs by 37 +/- 6%. Hence, synaptically released acetylcholine exerted a negative-feedback inhibition of coreleased glutamate. We conclude that most cholinergic basal forebrain neurons are capable of releasing glutamate as a cotransmitter and that the release of both transmitters is subject to simultaneous feedback inhibition by synaptically released acetylcholine. This has implications for BF neuron function and for the use of cholinesterase inhibitors in Alzheimer's disease.

Type: Article
Title: Simultaneous release of glutamate and acetylcholine from single magnocellular "cholinergic" basal forebrain neurons
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.3979-05.2006
Keywords: basal forebrain, cholinergic neuron, glutamate, acetylcholine (ACh), neurotransmitter, presynaptic regulation, RAT SYMPATHETIC NEURONS, RECEPTOR-MEDIATED INHIBITION, HIPPOCAMPAL PYRAMIDAL CELLS, ALZHEIMERS-DISEASE, SENILE-DEMENTIA, CEREBRAL-CORTEX, DIAGONAL BAND, NUCLEUS, CULTURE, MICROCULTURES
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/9492
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