ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Simultaneous release of glutamate and acetylcholine from single magnocellular "cholinergic" basal forebrain neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 81 citations in OpenAlex.
- Neuronal gene profiling of tau oligomer-bearing cholinergic nucleus basalis neurons during the onset of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Distinct synaptic mechanisms drive the behavioral response to acute stress and rapid correction by ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Linking temporal coordination of hippocampal activity to memory function.Frontiers in cellular neuroscience · 2023Review
- Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior.Brain structure & function · 2021Article
- Multi-Target Drug Candidates for Multifactorial Alzheimer's Disease: AChE and NMDAR as Molecular Targets.Molecular neurobiology · 2021Review
- A whole-brain map of long-range inputs to GABAergic interneurons in the mouse medial prefrontal cortex.Nature neuroscience · 2019Article
- Preferential cholinergic excitation of corticopontine neurons.The Journal of physiology · 2018Article
- Dual-transmitter systems regulating arousal, attention, learning and memory.Neuroscience and biobehavioral reviews · 2018Review
- Stereological Estimates of Glutamatergic, GABAergic, and Cholinergic Neurons in the Pedunculopontine and Laterodorsal Tegmental Nuclei in the Rat.Frontiers in neuroanatomy · 2018Article
- Article
- Local Optogenetic Induction of Fast (20-40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity.Frontiers in cellular neuroscience · 2016Article
- An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence.eLife · 2015Article
- Acetylcholine excites neocortical pyramidal neurons via nicotinic receptors.Journal of neurophysiology · 2015Article
- Hippocampal "cholinergic interneurons" visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation.Frontiers in synaptic neuroscience · 2015Article
- Multi-target design strategies in the context of Alzheimer's disease: acetylcholinesterase inhibition and NMDA receptor antagonism as the driving forces.Neurochemical research · 2014Review
- Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex.Frontiers in synaptic neuroscience · 2014Review
- Optogenetic studies of nicotinic contributions to cholinergic signaling in the central nervous system.Reviews in the neurosciences · 2014Review
- Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer's disease.Neurotoxicity research · 2013Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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 M2-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.
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