Simon Haziza

All Publications

• Prefrontal gamma oscillations engage dynamic cell type-specific configurations to support flexible behavior. bioRxiv : the preprint server for biology Phensy, A. J., Hagopian, L. L., Costello, C. M., Haziza, S., Ghenand, O., Zhang, Y., Schnitzer, M. J., Sohal, V. S. 2025

  Abstract

  Cognitive dysfunction in conditions such as schizophrenia involves disrupted communication between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). Parvalbumin interneurons (PVI) are known to regulate PFC microcircuits and generate gamma-frequency (~40Hz) oscillations - fast, synchronized neural rhythms that are recruited during many executive functions, necessary for cognitive flexibility, and deficient in schizophrenia. While targeting PVI-mediated gamma oscillations holds great therapeutic promise, their nature and specific functions, e.g., for regulating PFC→MD communication, remain elusive. Using dual-color voltage imaging and optogenetics, we reveal that PVIs dynamically entrain MD-projecting PFC neurons both locally and contralaterally, giving rise to multiple distinct circuit-specific patterns of distributed synchronization that are recruited in a behaviorally-specific manner to support particular aspects of flexible behavior. Thus, gamma oscillations are not unitary phenomena characterized by one microcircuit-wide pattern of entrainment. Rather, they comprise diverse motifs, defined by specific cell types and phase relationships, that are dynamically recruited for specific functions.

  View details for DOI 10.1101/2024.03.08.584173

  View details for PubMedID 40799566

  View details for PubMedCentralID PMC12340850

• Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals. Cell Haziza, S., Chrapkiewicz, R., Zhang, Y., Kruzhilin, V., Li, J., Li, J., Delamare, G., Swanson, R., Buzsaki, G., Kannan, M., Vasan, G., Lin, M. Z., Zeng, H., Daigle, T. L., Schnitzer, M. J. 2025

  Abstract

  Fluorescent genetically encoded voltage indicators report transmembrane potentials of targeted cell types. However, voltage-imaging instrumentation has lacked the sensitivity to track spontaneous or evoked high-frequency voltage oscillations in neural populations. Here, we describe two complementary TEMPO (transmembrane electrical measurements performed optically) voltage-sensing technologies that capture neural oscillations up to 100 Hz. Fiber-optic TEMPO achieves 10-fold greater sensitivity than prior photometric voltage sensing, allows hour-long recordings, and monitors two neuron classes per fiber-optic probe in freely moving mice. With it, we uncovered cross-frequency-coupled theta- and gamma-range oscillations and characterized excitatory-inhibitory neural dynamics during hippocampal ripples and visual cortical processing. The TEMPO mesoscope images voltage activity in two cell classes across an 8-mm-wide field of view in head-fixed animals. In awake mice, it revealed sensory-evoked excitatory-inhibitory neural interactions and traveling gamma and 3-7 Hz waves in visual cortex and bidirectional propagation directions for both hippocampal theta and beta waves. These technologies have widespread applications probing diverse oscillations and neuron-type interactions in healthy and diseased brains.

  View details for DOI 10.1016/j.cell.2025.06.028

  View details for PubMedID 40675148

• DYRK1A Up-Regulation Specifically Impairs a Presynaptic Form of Long-Term Potentiation LIFE-BASEL Lepagnol-Bestel, A., Haziza, S., Viard, J., Salin, P. A., Duchon, A., Herault, Y., Simonneau, M. 2025; 15 (2)

  Abstract

  Chromosome 21 DYRK1A kinase is associated with a variety of neuronal diseases including Down syndrome. However, the functional impact of this kinase at the synapse level remains unclear. We studied a mouse model that incorporated YAC 152F7 (570 kb), encoding six chromosome 21 genes including DYRK1A. The 152F7 mice displayed learning difficulties but their N-methyl-D-aspartate (NMDA)-dependent synaptic long-term potentiation is indistinguishable from non-transgenic animals. We have demonstrated that a presynaptic form of NMDA-independent long-term potentiation (LTP) at the hippocampal mossy fiber was impaired in the 152F7 animals. To obtain insights into the molecular mechanisms involved in such synaptic changes, we analyzed the Dyrk1a interactions with chromatin remodelers. We found that the number of DYRK1A-EP300 and DYRK1A-CREBPP increased in 152F7 mice. Moreover, we observed a transcriptional decrease in genes encoding presynaptic proteins involved in glutamate vesicle exocytosis, namely Rims1, Munc13-1, Syn2 and Rab3A.To refine our findings, we used a mouse BAC 189N3 (152 kb) line that only triplicates the gene Dyrk1a. Again, we found that this NMDA-independent form of LTP is impaired in this mouse line. Altogether, our results demonstrate that Dyrk1a up-regulation is sufficient to specifically inhibit the NMDA-independent form of LTP and suggest that this inhibition is linked to chromatin changes that deregulate genes encoding proteins involved in glutamate synaptic release.

  View details for DOI 10.3390/life15020149

  View details for Web of Science ID 001431113400001

  View details for PubMedID 40003558

  View details for PubMedCentralID PMC11856406

• Dual-polarity voltage imaging of the concurrent dynamics of multiple neuron types. Science (New York, N.Y.) Kannan, M., Vasan, G., Haziza, S., Huang, C., Chrapkiewicz, R., Luo, J., Cardin, J. A., Schnitzer, M. J., Pieribone, V. A. 2022; 378 (6619): eabm8797

  Abstract

  Genetically encoded fluorescent voltage indicators are ideally suited to reveal the millisecond-scale interactions among and between targeted cell populations. However, current indicators lack the requisite sensitivity for in vivo multipopulation imaging. We describe next-generation green and red voltage sensors, Ace-mNeon2 and VARNAM2, and their reverse response-polarity variants pAce and pAceR. Our indicators enable 0.4- to 1-kilohertz voltage recordings from >50 spiking neurons per field of view in awake mice and ~30-minute continuous imaging in flies. Using dual-polarity multiplexed imaging, we uncovered brain state-dependent antagonism between neocortical somatostatin-expressing (SST+) and vasoactive intestinal peptide-expressing (VIP+) interneurons and contributions to hippocampal field potentials from cell ensembles with distinct axonal projections. By combining three mutually compatible indicators, we performed simultaneous triple-population imaging. These approaches will empower investigations of the dynamic interplay between neuronal subclasses at single-spike resolution.

  View details for DOI 10.1126/science.abm8797

  View details for PubMedID 36378956

• Fast, in vivo voltage imaging using a red fluorescent indicator. Nature methods Kannan, M., Vasan, G., Huang, C., Haziza, S., Li, J. Z., Inan, H., Schnitzer, M. J., Pieribone, V. A. 2018

  Abstract

  Genetically encoded voltage indicators (GEVIs) are emerging optical tools for acquiring brain-wide cell-type-specific functional data at unparalleled temporal resolution. To broaden the application of GEVIs in high-speed multispectral imaging, we used a high-throughput strategy to develop voltage-activated red neuronal activity monitor (VARNAM), a fusion of the fast Acetabularia opsin and the bright red fluorophore mRuby3. Imageable under the modest illumination intensities required by bright green probes (<50mWmm-2), VARNAM is readily usable in vivo. VARNAM can be combined with blue-shifted optical tools to enable cell-type-specific all-optical electrophysiology and dual-color spike imaging in acute brain slices and live Drosophila. With enhanced sensitivity to subthreshold voltages, VARNAM resolves postsynaptic potentials in slices and cortical and hippocampal rhythms in freely behaving mice. Together, VARNAM lends a new hue to the optical toolbox, opening the door to high-speed in vivo multispectral functional imaging.

  View details for PubMedID 30420685

• Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors NATURE NANOTECHNOLOGY Haziza, S., Mohan, N., Loe-Mie, Y., Lepagnol-Bestel, A., Massou, S., Adam, M., Le, X., Viard, J., Plancon, C., Daudin, R., Koebel, P., Dorard, E., Rose, C., Hsieh, F., Wu, C., Potier, B., Herault, Y., Sala, C., Corvin, A., Allinquant, B., Chang, H., Treussart, F., Simonneau, M. 2017; 12 (4): 322–28

  Abstract

  Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

  View details for DOI 10.1038/NNANO.2016.260

  View details for Web of Science ID 000398767500012

  View details for PubMedID 27893730

• Single particle tracking of fluorescent nanodiamonds in cells and organisms CURRENT OPINION IN SOLID STATE & MATERIALS SCIENCE Hui, Y., Hsiao, W., Haziza, S., Simonneau, M., Treussart, F., Chang, H. 2017; 21 (1): 35–42

  View details for DOI 10.1016/j.cossms.2016.04.002

  View details for Web of Science ID 000396954200005