The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons
Abstract
The reticular thalamic nucleus (RTN) of the mouse is characterized by an overwhelming majority of GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections mainly on thalamocortical neurons. The RTN neurons express high levels of the “slow Ca 2+ buffer” parvalbumin (PV) and are characterized by low-threshold Ca 2+ currents, I T . We performed extracellular recordings in ketamine/xylazine anesthetized mice in the rostromedial portion of the RTN. In the RTN of wild-type and PV knockout (PVKO) mice we distinguished four types of neurons characterized on the basis of their firing pattern: irregular firing (type I), medium bursting (type II), long bursting (type III), and tonically firing (type IV). Compared with wild-type mice, we observed in the PVKOs the medium bursting (type II) more frequently than the long bursting type and longer interspike intervals within the burst without affecting the number of spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated with the kinetics of burst discharges. Ca v 3.2 channels, which mediate the I T currents, were more localized to the somatic plasma membrane of RTN neurons in PVKO mice, whereas Ca v 3.3 expression was similar in both genotypes. The immunoelectron microscopy analysis showed that Ca v 3.2 channels were localized at active axosomatic synapses, thus suggesting that the differential localization of Ca v 3.2 in the PVKOs may affect bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip showed that about one-third of the cell pairs tended to fire synchronously in both genotypes, independent of PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons but affects the distribution of Ca v 3.2 channels and the dynamics of burst discharges of RTN cells, which in turn regulate the activity in the thalamocortical circuit.
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The demonstration that PV levels are decreased may indicate a shift in the E/I balance towards increased inhibition, taking into account the proven role of PV in synaptic transmission.
“In addition, the demonstration that PV levels are decreased may indicate a shift in the E/I balance towards an increased inhibition, taking into account the proven role of PV in synaptic transmission [52, 53, 55, 97, 98].”
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Filice, F., Vörckel, K. J., Sungur, A. Ö., Wöhr, M., & Schwaller, B. (2016) · Molecular Brain · doi:10.1186/s13041-016-0192-8 · Cited by 240 · see citing works
“In addition, the demonstration that PV levels are decreased may indicate a shift in the E/I balance towards an increased inhibition, taking into account the proven role of PV in synaptic transmission [52, 53, 55, 97, 98].”
BackgroundSelf-citationWöhr, M., Orduz, D., Gregory, P., Moreno, H., Khan, U., Vörckel, K. J., Wolfer, D. P., Welzl, H., Gall, D., Schiffmann, S. N., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.19 · Cited by 258 · see citing works
Self-citationCohen, S. M., Tsien, R. W., GOFF, D. C., & Halassa, M. M. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2014.12.026 · Cited by 233 · see citing works
“…expression of parvalbumin (PV) (Kinney et al., 2006), a Ca2+ binding protein that defines a subpopulation of inhibitory neurons andmodulates its firing properties (shown in the thalamic reticular nucleus [TRN]; Albéri et al., 2013) and plasticity (shown in the cerebellum; Caillard et al., 2000).”
BackgroundGABAergic Function as a Limiting Factor for Prefrontal Maturation during Adolescence
Caballero, A. C., & Tseng, K. Y. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.04.010 · Cited by 178 · see citing works
Physiology of intracellular calcium buffering
Eisner, D. A., Neher, E., Taschenberger, H., & Smith, G. L. (2023) · Physiological Reviews · doi:10.1152/physrev.00042.2022 · Cited by 158 · see citing works
The Parvalbumin Hypothesis of Autism Spectrum Disorder
Filice, F., Janickova, L., Henzi, T., Bilella, A., & Schwaller, B. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.577525 · Cited by 112 · see citing works
“Additionally, the ISI within a burst was longer, while the number of spikes was unaffected (Alberi et al., 2013).”
BackgroundSelf-citationCytosolic Ca 2+ Buffers Are Inherently Ca 2+ Signal ModulatorsPreprint
Schwaller, B. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035543 · Cited by 89 · see citing works
“The observed changes in the RTN firing properties (as seen in PVmice; Albéri et al. 2013) may hint that the decrease in PV RTNneurons being the result of PV down-regulation.”
BackgroundSelf-citationCortical Circuit Dysfunction as a Potential Driver of Amyotrophic Lateral Sclerosis
Brunet, A., Stuart‐Lopez, G., Burg, T., Scekic‐Zahirovic, J., & Rouaux, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00363 · Cited by 66 · see citing works
Cerebellins are differentially expressed in selective subsets of neurons throughout the brain
Seigneur, E. M., & Südhof, T. C. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24278 · Cited by 69 · see citing works
Incubation of depression: ECM assembly and parvalbumin interneurons after stress
Spijker, S., Koskinen, M.-K., & Riga, D. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.07.015 · Cited by 55 · see citing works
Bicker, F., Vasić, V., Horta, G., Ortega, F., Nolte, H., Kavyanifar, A., Keller, S., Stanković, N. D., Harter, P. N., Benedito, R., et al. (2017) · Nature Communications · doi:10.1038/ncomms15922 · Cited by 36 · see citing works
Experience-dependent plasticity of gustatory insular cortex circuits and taste preferences
Schiff, H. C., Kogan, J. F., Isaac, M., Czarnecki, L. A., Fontanini, A., & Maffei, A. (2023) · Science Advances · doi:10.1126/sciadv.ade6561 · Cited by 37 · see citing works
“Last, PV regulates firing properties of GABA neurons in the thalamic reticular nucleus (59).”
BackgroundLiu, J., Zhang, M., Wu, X., Lazarus, M., Chérasse, Y., Yuan, M.-Y., Huang, Z., & Li, R. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.10.013 · Cited by 32 · see citing works
Viena, T. D., Rasch, G. E., da Silva, D. M., & Allen, T. A. (2020) · Hippocampus · doi:10.1002/hipo.23271 · Cited by 30 · see citing works
“The lack of PV expression in midline thalamic cells stood in stark contrast to prominent PV + cell body labeling in other brain regions with well-established PV + cell populations including the thalamic reticular nucleus of the thalamus (TRN), the hippocampus, lateral and basolateral amygdala, striatum, and cortex (Fi…”
BackgroundDougherty, S., Bartley, A. F., Lucas, E. K., Hablitz, J. J., Dobrunz, L. E., & Cowell, R. M. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.023 · Cited by 28 · see citing works
“A loss of PV itself could contribute to the decreased firing rate, as loss of the calcium buffer in PV knockout mice has been shown to alter intrinsic excitability of GABAergic neurons in the reticular thalamic nucleus (Alberi et al., 2013).”
Mongrédien, R., Erdozain, A. M., Dumas, S., Cutando, L., Nuñez-delMoral, A., Puighermanal, E., Amin, S. R., Bruno Giros, A., Valjent, E., Meana, J. J., et al. (2019) · Brain Structure and Function · doi:10.1007/s00429-019-01831-x · Cited by 27 · see citing works
The role of thalamic nuclei in genetic generalized epilepsies
Lüttjohann, A., & van Luijtelaar, G. (2022) · Epilepsy Research · doi:10.1016/j.eplepsyres.2022.106918 · Cited by 26 · see citing works
Brandenburg, C., Smith, L. A., Kilander, M. B. C., Bridi, M. S., Lin, Y., Huang, S., & Blatt, G. J. (2021) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2021.103650 · Cited by 24 · see citing works
“PV is known to contribute to a cell's capacity for high firing rates through its function as a calcium binding protein (e.g. Albéri et al., 2013; Rainnie et al., 2006).”
BackgroundMcMeekin, L. J., Joyce, K. L., Jenkins, L. M. M., Bohannon, B. M., Patel, K. D., Bohannon, A. S., Patel, A., Fox, S. N., Simmons, M. S., Day, J. J., et al. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.10.007 · Cited by 23 · see citing works
Notch1 activity in the olfactory bulb is odour‐dependent and contributes to olfactory behaviour
Brai, E., Marathe, S., Zentilin, L., Giacca, M., Nimpf, J., Kretz, R., Scotti, A., & Alberi, L. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12719 · Cited by 22 · see citing works
Self-citationSchizophrenia: from neurophysiological abnormalities to clinical symptoms
Castelnovo, A., Ferrarelli, F., & D’Agostino, A. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.00478 · Cited by 21 · see citing works
“PV deficiency affects the dynamics of burst discharges of TRN cells, which in turn regulate the activity in the thalamocortical circuit (Albéri et al., 2013).”
Jorgensen, E. T., Gonzalez, A. E., Harkness, J. H., Hegarty, D. M., Thakar, A., Burchi, D. J., Aadland, J. A., Aicher, S. A., Sorg, B. A., & Brown, T. E. (2020) · Addiction Biology · doi:10.1111/adb.12947 · Cited by 20 · see citing works
Hughes, R. B., Whittingham-Dowd, J., Simmons, R. E., Clapcote, S., Broughton, S. J., & Dawson, N. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhz244 · Cited by 17 · see citing works
“This suggestion is further supported by the observation that parvalbumin directly regulates neuronal activity in the RT (Alberi et al. 2012).”
Attractor dynamics of a Boolean model of a brain circuit controlled by multiple parameters
Cabessa, J., & Villa, A. E. P. (2018) · Chaos An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/1.5042312 · Cited by 17 · see citing works
Self-citationPopelář, J., Rybalko, N., Burianova, J. S., Schwaller, B., & Syka, J. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.08.042 · Cited by 17 · see citing works
Self-citationTsai, C., Tsai, S., Pan, Y., Lin, H.-M., Pan, T., & Yang, F. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01195-x · Cited by 13 · see citing works
Complex temporal patterns processing by a neural mass model of a cortical column
Malagarriga, D., Pons, A. J., & Villa, A. E. P. (2019) · Cognitive Neurodynamics · doi:10.1007/s11571-019-09531-2 · Cited by 13 · see citing works
Self-citationGABAergic Gene Regulatory Elements Used in Adeno-Associated Viral Vectors
Duba-Kiss, R., Niibori, Y., & Hampson, D. R. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.745159 · Cited by 12 · see citing works
“Examples include cortical basket and chandelier cells (60), some hippocampal interneurons (61), and interneurons in the reticular thalamic nucleus (62).”
BackgroundCross-species conservation in the regulation of parvalbumin by perineuronal nets
Wang, A. S., Wan, X., Storch, D.-S., Li, V. Y., Cornez, G., Balthazart, J., Cisneros-Franco, J. M., de Villers‐Sidani, E., & Sakata, J. T. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2023.1297643 · Cited by 12 · see citing works
Visual thalamocortical circuits in parvalbumin-deficient mice
Lintas, A., Schwaller, B., & Villa, A. E. P. (2013) · Brain Research · doi:10.1016/j.brainres.2013.04.048 · Cited by 12 · see citing works
Self-citationLintas, A., Sánchez‐Campusano, R., Villa, A. E. P., Gruart, A., & Delgado-Garcia, J. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-82519-3 · Cited by 10 · see citing works
Self-citationRethinking parvalbumin: From passive marker to active modulator of hippocampal circuits
Zhang, N., Hu, B., Li, X., & Huang, H. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.10.005 · Cited by 7 · see citing works
López-Canul, M., Oveisi, A., He, Q., Vigano, M., Farina, A., Comai, S., & Gobbi, G. (2025) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaf017 · Cited by 5 · see citing works
“58,59 The RTN is known to be involved in the generation of NREMS.”
Lintas, A. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.04.023 · Cited by 5 · see citing works
Self-citationParvalbumin protein controls inhibitory tone in the spinal cordPreprint
Qiu, H., Miraucourt, L. S., Petitjean, H., Davidova, A., Levesque-Damphousse, P., Estall, J. L., & Sharif‐Naeini, R. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.15.508019 · Cited by 4 · see citing works
Gruart, A., Delgado-Garcia, J. M., & Lintas, A. (2016) · Advances in cognitive neurodynamics · doi:10.1007/978-981-10-0207-6_17 · Cited by 3 · see citing works
Self-citationPerineuronal nets in motor circuitry regulate the performance of learned vocalizations in songbirds
Wan, X., Wang, A. S., Storch, D.-S., Li, V. Y., & Sakata, J. T. (2025) · Communications Biology · doi:10.1038/s42003-025-07520-2 · Cited by 2 · see citing works
Immunohistochemical distribution of secretagogin in the mouse brain
de Meneses, P. G. T., Pérez-Revuelta, L., Canal-Alonso, Á., Hernández-Pérez, C., Cocho, T., Valero, J., Weruaga, E., Díaz, D., & Alonso, J. R. (2023) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2023.1224342 · Cited by 2 · see citing works
“This particular distribution could be related to the fact that having the same protein in most of the cells allows the modulation of the firing rate, as it happens with PV in the reticular thalamic nucleus (Albéri et al., 2013).”
BackgroundCellular mechanisms regulating the timing of organizational effects of sex steroid hormones
Sakata, J. T., & Balthazart, J. (2026) · Hormones and Behavior · doi:10.1016/j.yhbeh.2026.105923 · Cited by 1 · see citing works
Changes in neuronal activity of the reticular thalamic nucleus in anaesthetized parkinsonian rats.
Little, S. T. C. (2015) · Otago University Research Archive (University of Otago)
Causal control of the thalamic reticular nucleus using optogenetic and novel chemogenetic approaches
Higashikubo, B. T. (2016) · DSpace@MIT (Massachusetts Institute of Technology)
Lintas, A., Abé, T., Villa, A. E. P., & Asai, Y. (2018) · Lecture notes in computer science · doi:10.1007/978-3-030-01421-6_38
“It has been reported that Granger causality cannot detect inhibitory connections with the same accuracy as excitatory ones [9], which could be a serious hindrance in our study because Calciumbinding protein expressed in GABAergic inhibitory neurons of the thalamic reticular nucleus, a brain structure playing a key rol…”
BackgroundSelf-citationParvalbumin阳性中间神经元缺陷在精神分裂症病理机制中的作用
Deng, X., & Guo, J. (2018) · Advances in Psychological Science · doi:10.3724/sp.j.1042.2018.01992
Non-canonical role of DNA mismatch repair on sensory processing in mice
Rahman, S., Neophytou, D., Oviedo-Gray, S., Vuong, B. Q., & Oviedo, H. V. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.12.066
Neurobiology of Saccadic Neurons in Monkeys
Horn, A. K. E., Mayadali, Ü. S., Kuhn, K. S., Abspacher, M., & Shaikh, A. G. (2026) · Contemporary clinical neuroscience · doi:10.1007/978-3-032-07539-0_25
Rôle de la protéine matricellulaire hevin dans la réponse à la cocaïne
Mongrédien, R. (2018) · theses.fr (ABES) · doi:10.70675/926d644czef3bz4ce3z9fd7z6080a7628079
Responsiveness and dynamics of asynchronous states and Gamma oscillations in cerebral cortex
Susin, E. (2021) · theses.fr (ABES) · doi:10.70675/45a9917bz0609z450azbd4bz82094b558df6
Seif, P. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106897
- Authors
- Albéri, L., Lintas, A., Kretz, R., Schwaller, B., & Villa, A. E. P.
- Affiliations
- Unit of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland; and
- University of Fribourg (CH)
- University of Lausanne (CH)
- Corresponding author
- Villa, Alessandro E. P.
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2013-06-01
- Volume
- 109
- Issue
- 11
- Pages
- 2827-2841
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2084755356
- Cited by
- 49
- References
- 105
- Citations by year
- 2026: 3 · 2025: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 2
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Universität Heidelberg
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- parvalbumin, thalamic reticular nucleus, bursting neurons, low-threshold calcium current, calcium buffering, neuronal firing patterns, axosomatic synapses, neuronal synchronization, thalamocortical circuits, GABAergic neurons
- MeSH terms
- Action Potentials, Animals, Axons, Calcium, Genotype, Mice, Inbred C57BL, Neurons, Parvalbumins, Synapses, Intralaminar Thalamic Nuclei, Calcium Channels, T-Type, Protein Transport, Mice
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