Fast synaptic subcortical control of hippocampal circuits
Abstract
Cortical information processing is under state-dependent control of subcortical neuromodulatory systems. Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible. Yet, it is currently unknown if any such form of subcortical control exists. Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center. Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons. At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit. This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function.
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Median raphe 5-HT/vGluT3+ neurons activate CA1 inhibitory interneurons to disynaptically inhibit CA1 pyramidal neurons.
“Compounding the diverse and extensive functions of 5-HT neurons, median raphe 5-HT/vGluT3+ neurons also activate CA1 inhibitory interneurons to disynaptically inhibit CA1 pyramidal neurons.81”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [81]
Glutamate co-release from Vglut3+ serotonin terminals has been reported at the hippocampus, orbital prefrontal cortex, nucleus accumbens, ventral tegmental area, and basolateral amygdala.
“Glutamate co-release from Vglut3+ serotonin terminals has indeed been reported at the hippocampus (Varga et al., 2009), orbital prefrontal cortex (Ren et al., 2018), nucleus accumbens (Liu et al., 2014), ventral tegmental area (Wang et al., 2019), and basolateral amygdala (Sengupta et al., 2017).”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Varga et al., 2009
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References 19 · Cited by 248
- Authors
- Varga, V., Losonczy, A., Zemelman, B. V., Borhegyi, Z., Nyiri, G., Domonkos, A., Hangya, B., Holderith, N., Magee, J. C., & Freund, T. F.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Howard Hughes Medical Institute (US)
- Institute of Experimental Medicine, Budapest 1083, Hungary.
- Corresponding author
- Varga, Viktor
- Losonczy, Attila
- Zemelman, Boris V.
- ORCID
- Venue
- Science
- Published
- 2009-10-16
- Volume
- 326
- Issue
- 5951
- Pages
- 449-453
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2039338324
- Cited by
- 248
- References
- 19
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 11 · 2023: 18 · 2022: 14 · 2021: 12 · 2020: 13 · 2019: 12 · 2018: 10 · 2017: 15 · 2016: 20 · 2015: 17 · 2014: 21 · 2013: 8 · 2012: 18
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (HHMI55005608)
- National Institute of Mental Health (R01MH054671, MH54671)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampal circuitry, synaptic transmission, hippocampal interneurons, GABAergic inhibition, disynaptic inhibition
- MeSH terms
- Animals, Electric Stimulation, Hippocampus, Interneurons, Neural Inhibition, Neural Pathways, Neurons, Afferent, Photic Stimulation, Raphe Nuclei, Serotonin, Synapses, Rats, Sprague-Dawley, Patch-Clamp Techniques, Glutamic Acid, Excitatory Postsynaptic Potentials, Mice, Rats, Inhibitory Postsynaptic Potentials, Synaptic Potentials
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