Activity Deprivation Reduces Miniature IPSC Amplitude by Decreasing the Number of Postsynaptic GABA A Receptors Clustered at Neocortical Synapses
Open accessAbstract
Maintaining the proper balance between excitation and inhibition is necessary to prevent cortical circuits from either falling silent or generating epileptiform activity. One mechanism through which cortical networks maintain this balance is through the activity-dependent regulation of inhibition, but whether this is achieved primarily through changes in synapse number or synaptic strength is not clear. Previously, we found that 2 d of activity deprivation increased the amplitude of miniature EPSCs (mEPSCs) onto cultured visual cortical pyramidal neurons. Here we find that this same manipulation decreases the amplitude of mIPSCs. This occurs with no change in single-channel conductance but is accompanied by a reduction in the average number of channels open during the mIPSC peak and a reduction in the intensity of staining for GABAA receptors (GABAARs) at postsynaptic sites. In addition, the number of synaptic sites that express detectable levels of GABAARs was decreased by ∼50% after activity blockade, although there was no reduction in the total number of presynaptic contacts. These data suggest that activity deprivation reduces cortical inhibition by reducing both the number of GABAARs clustered at synaptic sites and the number of functional inhibitory synapses. Because excitatory and inhibitory synaptic currents are regulated in opposite directions by activity blockade, these data suggest that the balance between excitation and inhibition is dynamically regulated by ongoing activity.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Homeostatic regulation of inhibition involves coordinated changes in postsynaptic strength, synapse number, and likely presynaptic release probability.
“Interestingly, both in vitro and in vivo studies have documented that homeostatic regulation of inhibition involves coordinated changes in postsynaptic strength, synapse number, and likely presynaptic release probability (Kilman et al. 2002;Maffei et al. 2004;Hartman et al. 2006).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Kilman et al. 2002
The Abstract (page unavailable) reports that activity deprivation reduced mIPSC amplitude and the number of sites with detectable postsynaptic GABA_A receptors, supporting coordinated changes in postsynaptic strength and functional inhibitory synapse number. It also says total presynaptic contacts were unchanged. The paper does not establish a change in presynaptic release probability, so that part of the jointly cited claim is not supported by Kilman et al. (LLM, conf=0.88)
Experimental — accuracy not yet measuredInhibitory synapses onto pyramidal neurons are regulated in the opposite direction from excitatory synapses in response to a drop in activity or sensory drive, both in vitro and in vivo.
“Further, it has been shown both in vitro and in vivo that inhibitory synapses onto pyramidal neurons are regulated in the opposite direction from excitatory synapses in response to a drop in activity or sensory drive (Kilman et al. 2002;Vale and Sanes 2002;Maffei et al. 2004;Hartman et al. 2006;Huupponen et al. 2007).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Kilman et al. 2002
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stability of the memory of eye position in a recurrent network of conductance-based model neurons
Seung, H. S., Lee, D. D., Reis, B. Y., & Tank, D. W. (2000) · Neuron · doi:10.1016/s0896-6273(00)81155-1 · Cited by 339 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Homeostatic plasticity in the developing nervous system
Turrigiano, G. G., & Nelson, S. B. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1327 · Cited by 2,485 · see citing works
Self-citationThe self-tuning neuron: synaptic scaling of excitatory synapses
Turrigiano, G. G. (2008) · Cell · doi:10.1016/j.cell.2008.10.008 · Cited by 1,533 · see citing works
Self-citationA translational profiling approach for the molecular characterization of CNS cell types
Heiman, M., Schaefer, A., Gong, S., Peterson, J. D., Day, M., Ramsey, K. E., Suárez-Fariñas, M., Schwarz, C., Stephan, D. A., Surmeier, D. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.028 · Cited by 1,134 · see citing works
Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function
Turrigiano, G. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005736 · Cited by 1,139 · see citing works
Self-citationDifferential Regulation of AMPA Receptor and GABA Receptor Trafficking by Tumor Necrosis Factor-α
Stellwagen, D., Beattie, E. C., Seo, J. Y., & Malenka, R. C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4486-04.2005 · Cited by 985 · see citing works
“Specifically, when circuit activity is pharmacologically reduced, excitatory synapses are strengthened and inhibitory synapses weakened (Turrigiano and Nelson, 2004), at least in part through changes in the synaptic surface expression of AMPARs and GABAA receptors (Kilman et al., 2002; Turrigiano and Nelson, 2004).”
BackgroundToo many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement
Turrigiano, G. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153238 · Cited by 671 · see citing works
Self-citationUnraveling mechanisms of homeostatic synaptic plasticity
Pozo, K., & Goda, Y. (2010) · Neuron · doi:10.1016/j.neuron.2010.04.028 · Cited by 565 · see citing works
HOMEOSTATIC CONTROL OF NEURAL ACTIVITY: From Phenomenology to Molecular Design
Davis, G. W. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135751 · Cited by 543 · see citing works
Taverna, S., Ilijic, E., & Surmeier, D. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5493-07.2008 · Cited by 399 · see citing works
Liu, G. (2004) · Nature Neuroscience · doi:10.1038/nn1206 · Cited by 339 · see citing works
Postsynaptic expression of homeostatic plasticity at neocortical synapses
Wierenga, C. J., Ibata, K., & Turrigiano, G. G. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5217-04.2005 · Cited by 306 · see citing works
Self-citationKullmann, D. M., Moreau, A. W., Bakiri, Y., & Nicholson, E. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.030 · Cited by 234 · see citing works
Rapid critical period induction by tonic inhibition in visual cortex
Iwai, Y., Fagiolini, M., Obata, K., & Hensch, T. K. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06695.2003 · Cited by 201 · see citing works
Adult neurogenesis modifies excitability of the dentate gyrus
Ikrar, T., Guo, N., He, K., Besnard, A., Levinson, S., Hill, A., Lee, H.-K., Hen, R., Xu, X., & Sahay, A. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00204 · Cited by 192 · see citing works
Homeostatic regulation of AMPA receptor expression at single hippocampal synapses
Hou, Q., Zhang, D., Jarzylo, L., Huganir, R. L., & Man, H.-Y. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706447105 · Cited by 179 · see citing works
Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses
Kim, J., & Alger, B. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2517 · Cited by 149 · see citing works
A review of hyperacusis and future directions: part II. Measurement, mechanisms, and treatment
Pienkowski, M., Tyler, R. S., Roncancio, E. R., Jun, H. J., Brozoski, T., Dauman, N., Coelho, C. B., Andersson, G., Keiner, A. J., Cacace, A. T., et al. (2014) · American Journal of Audiology · doi:10.1044/2014_aja-13-0037 · Cited by 138 · see citing works
Lazarus, M. S., Krishnan, K., & Huang, Z. J. (2015) · Cerebral Cortex · doi:10.1093/cercor/bht322 · Cited by 109 · see citing works
Neuroimmune regulation of homeostatic synaptic plasticity
Pribiag, H., & Stellwagen, D. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.008 · Cited by 106 · see citing works
Joseph, A., & Turrigiano, G. G. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.0618-17.2017 · Cited by 94 · see citing works
Self-citationInstructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons
Ye, Z., Mostajo-Radji, M. A., Brown, J. R., Rouaux, C., Tomassy, G. S., Hensch, T. K., & Arlotta, P. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.006 · Cited by 73 · see citing works
Chapman, C. A., Nuwer, J. L., & Jacob, T. C. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.911020 · Cited by 62 · see citing works
Mizoguchi, Y., Kanematsu, T., Hirata, M., & Nabekura, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305872200 · Cited by 59 · see citing works
Cantaut-Belarif, Y., Antri, M., Pizzarelli, R., Colasse, S., Vaccari, I., Soares, S., Renner, M., Dallel, R., Triller, A., & Bessis, A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201607048 · Cited by 56 · see citing works
Glausier, J. R., Kimoto, S., Fish, K. N., & Lewis, D. A. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.010 · Cited by 53 · see citing works
- Authors
- Kilman, V., van Rossum, M. C. W., & Turrigiano, G. G.
- Affiliations
- Brandeis University (US)
- ORCID
- Turrigiano, Gina G.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-02-15
- Volume
- 22
- Issue
- 4
- Pages
- 1328-1337
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4321429493
- Cited by
- 362
- References
- 1
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 19 · 2023: 12 · 2022: 11 · 2021: 9 · 2020: 15 · 2019: 11 · 2018: 9 · 2017: 21 · 2016: 16 · 2015: 16 · 2014: 16 · 2013: 19 · 2012: 18
- FWCI
- 6.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Science Foundation (9726944)
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01 NS-36853, K02 NS01893, R01NS036853)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- activity deprivation, miniature IPSCs, GABAA receptor, synaptic inhibition, excitation-inhibition balance, inhibitory synapses, visual cortex, pyramidal neurons, synaptic plasticity, single-channel conductance
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
