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Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum
Open accessAbstract
The dorsal striatum is a large forebrain region involved in action initiation, timing, control, learning and memory. Learning and remembering skilled movement sequences requires the dorsal striatum, and striatal subregions participate in both goal-directed (action-outcome) and habitual (stimulus-response) learning. Modulation of synaptic transmission plays a large part in controlling input to as well as the output from striatal medium spiny projection neurons (MSNs). Synapses in this brain region are subject to short-term modulation, including allosteric alterations in ion channel function and prominent presynaptic inhibition. Two forms of long-term synaptic plasticity have also been observed in striatum, long-term potentiation (LTP) and long-term depression (LTD). LTP at glutamatergic synapses onto MSNs involves activation of NMDA-type glutamate receptors and D1 dopamine or A2A adenosine receptors. Expression of LTP appears to involve postsynaptic mechanisms. LTD at glutamatergic synapses involves retrograde endocannabinoid signaling stimulated by activation of metabotropic glutamate receptors (mGluRs) and D2 dopamine receptors. While postsynaptic mechanisms participate in LTD induction, maintained expression involves presynaptic mechanisms. A similar form of LTD has also been observed at GABAergic synapses onto MSNs. Studies have just begun to examine the roles of synaptic plasticity in striatal-based learning. Findings to date indicate that molecules implicated in induction of plasticity participate in these forms of learning. Neurotransmitter receptors involved in LTP induction are necessary for proper skill and goal-directed instrumental learning. Interestingly, receptors involved in LTP and LTD at glutamatergic synapses onto MSNs of the "indirect pathway" appear to have important roles in habit learning. More work is needed to reveal if and when synaptic plasticity occurs during learning and if so what molecules and cellular processes, both short- and long-term, contribute to this plasticity.
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“It is believed that the interaction between glutamate and striatal activity serves as an important modulator of synaptic plasticity and neural excitability (Surmeier et al., 2007; Kreitzer et al., 2009; Lovinger et al., 2010; Gleich et al., 2015).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Lovinger et al., 2010
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“Altered dopamine signaling may impair reward processing, a key feature in AN, while also exacerbating compulsive behaviors in OC [48].”
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“While LTP enhances synaptic strength and LTD reduces it, both processes are regulated by changes in neurotransmitter release probabilities and receptor sensitivities (Lovinger 2010 ).”
Gong, S., Adler, J., Zhu, Y., Szeto, C., Lin, L., Rauffenbart, C., Torres-Herraez, A., Asher, W. B., Javitch, J. A., & Ford, C. (2026) · Science Advances · doi:10.1126/sciadv.aee6579
“D2Rs play a critical role in regulating striatal synaptic plasticity including the induction of LTP ( 66 – 72 ).”
Caudet-Pastor, C., López-Malo, D., & Luque-García, A. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1931282
“In PD, cortico-striatal synaptic plasticity is impaired, affecting both long-term potentiation (LTP) and long-term depression (LTD), which impacts learning and memory processes (Jin and Costa, 2015; Lovinger, 2010; Madadi Asl et al., 2022).”
dos Santos, B. C., da Rosa, I. V., MAZZARDO, L. D. F., Santos, N. D. S., Fabro, I. F., Nery, T., Bastos-Pereira, A. L., & Aguiar, A. S. (2026) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.6c00206
Metadata
- Authors
- Lovinger, D. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lovinger, David M.
- ORCID
- Lovinger, David M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 58
- Issue
- 7
- Pages
- 951-961
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC2849868
- OpenAlex
- W2086614467
- Cited by
- 488
- References
- 150
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 28 · 2023: 21 · 2022: 37 · 2021: 32 · 2020: 27 · 2019: 32 · 2018: 30 · 2017: 39 · 2016: 25 · 2015: 38 · 2014: 30 · 2013: 39 · 2012: 29
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000407)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dorsal striatum, synaptic plasticity, long-term potentiation, long-term depression, medium spiny neurons, glutamatergic synapses, GABAergic synapses, NMDA receptor, dopamine D1 receptor, adenosine A2A receptor, dopamine D2 receptor, metabotropic glutamate receptors, retrograde endocannabinoid signaling, presynaptic inhibition, allosteric modulation, operant conditioning, habit learning, goal-directed learning, indirect pathway, neurotransmitter receptors
- MeSH terms
- Animals, Corpus Striatum, Learning, Neuronal Plasticity, Synapses, Neurotransmitter Agents
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