CerCo
Centre de Recherche Cerveau & Cognition

Lionel G Nowak

Chargé de Recherche hors classe, CNRS
tel : 05 62 74 61 48, from abroad : +33 562 746 148

lionel.nowak@cnrs.fr
Team : neural DYNAmics of Memory and Object processing (DynaMO)

RESEARCH INTERESTS

My research is primarily based on in vivo and in vitro electrophysiological recording. This allows me to study the cellular mechanisms responsible for different aspects cortical function, as well as their short-term dynamics and plasticity, in healthy and pathological conditions.  Deciphering mechanisms implicates a multilevel approach to go beyond a mere description of brain phenomena.  The levels I encompass include

– the biochemical level (e.g., enzymatic control of neurotransmitter synthesis),
– the neuronal membrane level (intrinsic membrane properties),
– the synaptic level (interactions between neurons),
– the cellular level (action potentials, single-unit activity),
– the neuron population level (local field potential),
– and the dynamics at these different levels (development, adaptation, plasticity).

One of my main early activities has been the study of the structural bases and cellular mechanisms of visual perception. During my thesis, I studied the interactions between neurons belonging to different visual cortical areas apprehended by the cross-correlation method and the latency of visual responses in the visual cortex.  In parallel, I performed studies on rat brain slices in vitro; initially intended to study the synaptic features of corticocortical connections, this work drifted toward studies that revealed that axons, but not cell bodies, are activated by extracellular electrical stimulation in the cerebral gray matter.

During my postdoctoral research, I continued to use a dual in vivo/in vitro electrophysiology approach. Using primarily intracellular recording, I focused on analyzing neurons in terms of their intrinsic properties and synaptic responses, and on studying the mechanisms responsible for adaptation of the visual responses. I continued to study these questions after my return to France. We were able to establish the first fully quantitative classification of electrophysiological phenotypes in area 17 of the cat. We also examined orientation and direction selectivity in different electrophysiological neuronal classes. We also studied the transformation of the synaptic receptive field into a discharge receptive field and its consequences on spatial frequency selectivity. Etc.

During my postdoctoral research and beyond, I also focused on the study of the mechanisms and consequences of contrast adaptation. We were able to show that contrast adaptation depends on an intrinsic membrane mechanism, more precisely on the activation of a sodium-dependent potassium current, IK(Na). We then showed that neither GABAergic inhibition nor synaptic depression significantly intervene in contrast adaptation. Finally, we were able to establish that contrast adaptation is involved in the contrast invariance of orientation selectivity.

More recently I added a new level of study in my work, a “biochemical” level, initially by studying the role of an enzyme, tissue non-specific alkaline phosphatase (TNAP). This work has been done in close collaboration with Caroline Fonta (PresAge Team). Dysfunction of TNAP results in a disease called « hypophosphatasia ».  The main clinical sign of hypophosphatasia is a defective mineralization of the bone.  In addition, hypophosphatasia in its more severe forms is also characterized by epilepsia.  Using a mouse model of hypophosphatasia (Akp2 KO mice), we were able to confirm that TNAP plays an important role in the synthesis of GABA; we were also able to demonstrate that TNAP also plays a crucial role in the control of the concentration of extracellular purines (adenosine in particular), which, at the cortical level, are involved in the control of synaptic transmission and in short-term synaptic plasticity. We therefore examined the influence of adenosine on short-term synaptic plasticity in vitro. Studies carried out in vitro also allowed us to show that tetramisole, a TNAP inhibitor, has undesirable non-specific effects. Finally, we studied the role of TNAP in neuronal precursor cells proliferation and differentiation in the SK-N-SH neuroblastoma cell line.  We also examined alteration of lipid metabolism in TNAP KO mice.

We next examined the role of TNAP and purinergic system in the control of epilepsia in vitro.  I also contributed to analysis of single-unit activity obtained through intracerebral recording in humans.  This interest in epilepsia has led me to join the team Dynamo. I am also involved in a project aimed at establishing the role of serotonin in epilepsy associated with Alzheimer’s disease. My in vitro  studies should soon also be carried out on human brain slices.

My specialization also led to a collaboration with LAAS (MEMS team, CNRS-UPR 8001, Toulouse), which continues to this day, aimed at producing fully bioresorbable microelectrodes.

PUBLICATIONS (by topics)

Recent pdfs here: https://hal.science/search/index/?qa%5BauthFullName_t%5D%5B%5D=lionel+nowak&rows=30&labStructName_t=centre+de+recherche+cerveau+et+cognition&sort=producedDate_tdate+desc

Older pdfs : ask me !

Intracerebral single-unit recording in human epileptic patients
  • Despouy, E., Curot, J., Reddy, L., Nowak, L. G., Deudon, M., Sol, J. C., Lotterie, J. A., Denuelle, M., Maziz, A., Bergaud, C., Thorpe, S. J., Valton, L. and Barbeau, E. J. (2020) Recording local field potential and neuronal activity with tetrodes in epileptic patients. Journal of Neuroscience Methods 341, 108759. doi: 10.1016/j.jneumeth.2020.108759.
  • Despouy, E., Curot, J., Denuelle, M., Deudon, M., Sol, J. C., Lotterie, J. A., Reddy, L., Nowak, L. G., Pariente, J., Thorpe, S. J., Valton, L. and Barbeau, E. J. (2019) Neuronal spiking activity highlights a gradient of epileptogenicity in human tuberous sclerosis lesions. Clinical Neurophysiology 130, 537-547. doi: 10.1016/j.clinph.2018.12.013.
Tissue Non-specific Alkaline Phosphatase and the brain (TNAP)
  • Briolay, A., Nowak, L. G., Balayssac, S., Gilard, V., Magne, D. and Fonta, C. (2025) Tissue-nonspecific alkaline phosphatase promotes neuronal cell proliferation and differentiation: metabolomic discloses glutathione and taurine as molecular correlates.  Submitted to Journal of Neurochemistry August 5, 2025.  Ms number: JNC-2025-0668.
  • Gleizes, M., Fonta, C. and Nowak, L. G. (2022) Inhibitors of ectonucleotidases have paradoxical effects on synaptic transmission in the mouse cortex.  Journal of Neurochemistry 160, 305-324. doi: 10.1111/jnc.15558.
  • Cruz, T., Gleizes, M., Balayssac, S., Mornet, E., Marsal, G., Millán, J. L., Malet-Martino, M., Nowak, L. G., Gilard, V. and Fonta, C. (2017) Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR-based metabolomics analysis. Journal of Neurochemistry 140, 919-940. doi: 10.1111/jnc.13950.
  • Nowak, L. G., Rosay, B., Czégé, D. and Fonta, C. (2015) Tetramisole and levamisole suppress neuronal activity independently from their inhibitory action on tissue non-specific alkaline phosphatase in mouse cortex. Subcellular Biochemistry 76, 239-281. doi: 10.1007/978-94-017-7197-9_12.
Short-term synaptic plasticity, its modulation and why it is different in vitro compared to in vivo
  • Perrier, S. P., Gleizes, M., Fonta, C. and Nowak, L. G. (2019) Effect of adenosine on short-term synaptic plasticity in mouse piriform cortex in vitro: adenosine acts as a high-pass filter.  Physiological Reports, 7(3), e13992. doi: 10.14814/phy2.13992.
  • Gleizes, M., Perrier, S. P., Fonta, C. and Nowak, L. G. (2017) Prominent facilitation at beta and gamma frequency range revealed with physiological calcium concentration in adult mouse piriform cortex in vitro.  PlosOne 12(8), e0183246. doi: 10.1371/journal.pone.0183246.
  • Reig R, Gallego R, Nowak LG, and Sanchez-Vives MV (2006) Impact of cortical network activity on short-term synaptic depression. Cerebral Cortex 16, 688-695. doi: 10.1093/cercor/bhj014.
Cross modal interaction and plasticity
  • Vittek, A. L., Juan, C., Nowak, L. G., Girard, P. and Cappe, C. (2023) Multisensory integration in neurons of the medial pulvinar of macaque monkey. Cerebral Cortex 33, 4202-4215. doi: 10.1093/cercor/bhac337.
  • Sanchez-Vives MV, Nowak LG, Descalzo VF, Garcia-Velasco V, Gallego R, and Berbel P (2006) Cross modal audio-visual interactions in the primary visual cortex of the visually deprived cat: a physiological and anatomical study. Progress in Brain Research 155, 287-311.  doi: 10.1016/S0079-6123(06)55017-4.
New microelectrode designs for better compliance with brain tissue
  • Cointe, C., Laborde, A., Nowak, L. G., Arvanitis, D. N., Bourrier, D., Bergaud, C. and Maziz, A. (2022) Scalable batch fabrication of ultrathin flexible neural probes using bioresorbable silk layer.  Microsystems & Nanoengineering 8, 21. doi: 10.1038/s41378-022-00353-7. 
  • Vajrala, V. S., Saunier, V., Nowak, L. G., Flahaut, E., Bergaud, C. Maziz, A. (2021) Nanofibrous PEDOT-carbon composite on flexible probes for improved soft neural interfacing. Frontiers in Bioengineering and Biotechnology 9, 780197. doi: 10.3389/fbioe.2021.780197.
  • Vajrala, V. S., Saunier, V., Nowak, L., Flahaut, E., Bergaud, C., Maziz, A. (2021) Carbon Nanofiber/PEDOT Based Macro-Porous Composite for High Performance Multifunctional Neural Microelectrode.  ECS Transactions 104(2), 3, 2021. doi: 10.1149/10402.0003ecst
  • Castagnola, V., Descamps, E., Lecestre, A., Dahan, L., Remaud, J., Nowak, L. G. and Bergaud, C. (2015) Parylene-based flexible neural probes with PEDOT coated surface for brain stimulation and recording. Biosensors and Bioelectronics 67, 450-457. doi: 10.1016/j.bios.2014.09.004.
Mechanisms and consequences of contrast gain control and contrast adaptation in the visual cortex
  • Durand JB, Girard P, Barone P, Bullier J and Nowak LG (2012) Effects of contrast and contrast adaptation on static receptive field features in macaque area V1. Journal of Neurophysiology 108, 2033-2050.  doi: 10.1152/jn.00936.2011.
  • Persi E, Hansel D, Nowak L, Barone P and van Vreeswijk C (2011) Power-law input-output transfer functions explain the contrast-response and tuning properties of neurons in visual cortex. PLoS Computational Biology 7 : e1001078. doi: 10.1371/journal.pcbi.1001078.
  • Nowak LG and Barone P (2009) Contrast adaptation contributes to contrast-invariance of orientation tuning of primate V1 cells. PLoS one 4 : e4781. doi: 10.1371/journal.pone.0004781.
  • Descalzo VF, Nowak LG, Brumberg JC, McCormick DA and Sanchez-Vives MV (2005) Slow adaptation in fast spiking neurons of visual cortex. Journal of Neurophysiology 93, 1111-1118. doi: 10.1152/jn.00658.2004.
  • Nowak LG, Sanchez-Vives MV and McCormick DA (2005) Role of synaptic and intrinsic membrane properties in short term receptive field dynamics in cat area 17. Journal of Neuroscience 25, 1866-1880. doi: 10.1152/jn.00580.2002.
  • Sanchez-Vives MV*, Nowak LG* and McCormick DA (2000) Membrane mechanisms underlying contrast adaptation in cat area 17 in vivo. Journal of Neuroscience 20, 4267-4285. (* : shared first authorship) doi: 10.1523/JNEUROSCI.20-11-04267.2000.
  • Sanchez-Vives MV, Nowak LG and McCormick DA (2000) Cellular mechanisms of long lasting adaptation in visual cortical neurons in vitro. Journal of Neuroscience 20, 4286-4299. doi: 10.1523/JNEUROSCI.20-11-04286.2000.
Electrophysiological cell classes and receptive field properties (and their subthreshold mechanisms) in the visual cortex
  • Nowak LG, Sanchez-Vives MV and McCormick DA (2010) Spatial and temporal features of synaptic to discharge receptive field transformation in cat area 17. Journal of Neurophysiology 103, 677-697. doi: 10.1152/jn.90946.2008.
  • Nowak LG, Sanchez-Vives MV and McCormick DA (2008) Lack of orientation and direction selectivity in a subgroup of fast-spiking inhibitory interneurons : cellular and synaptic mechanisms and comparison with other electrophysiological cell types. Cerebral Cortex 18, 1058-1078. doi: 10.1093/cercor/bhm137.
  • Nowak LG, Sanchez-Vives MV, Azouz R, Gray CM and McCormick DA (2003) Electrophysiological classes of cat primary visual cortical neurons in vivo as revealed by quantitative analysis. Journal of Neurophysiology 89, 1541-1566. doi: 10.1152/jn.00580.2002.
  • Brumberg JC, Nowak LG and McCormick DA (2000) Ionic mechanisms underlying repetitive high-frequency burst firing in supragranular cortical neurons. Journal of Neuroscience 20, 4829-4843. doi: 10.1523/JNEUROSCI.20-13-04829.2000.
  • Azouz R, Gray CM, Nowak LG and McCormick, DA (1997) Physiological properties of identified interneurons in cat striate cortex. Cerebral Cortex 7, 534-545. doi: 10.1093/cercor/7.6.534.
Response latencies in primate visual cortex and what it implies concerning the hierarchical / parallel organization of the visual system
  • Nowak LG and Bullier J (1997) The timing of information transfer in the visual system. In : Cerebral Cortex vol. 12 : Extrastriate cortex in primates, K. Rockland, J.H. Kaas and A. Peters (eds), pp. 205-241.
  • Bullier J and Nowak LG (1995) Parallel versus serial processing, new vistas on the distributed organization of the visual system. Current Opinion in Neurobiology 5, 497-503. doi: 10.1016/0959-4388(95)80011-5.
  • Munk MHJ, Nowak LG, Girard P, Chounlamountri N and Bullier J (1995) Visual latencies in different cytochrome oxidase bands of macaque monkey area V2. Proceedings of the National Academy of Science of the USA 92, 988-992. doi: 10.1073/pnas.92.4.988.
  • Nowak LG, Munk MHJ, Girard P and Bullier J (1995) Visual latencies in areas V1 and V2 of the macaque monkey. Visual Neuroscience 12, 371-384. doi: 10.1017/s095252380000804x.
Synchronization of neuronal activities in vivo and spike timing reliability in vitro
  • Nowak LG and Bullier J (2000) Cross correlograms for neuronal spike trains. Different types of temporal correlation in neocortex, their origin and significance. In : Time and the Brain (ISBN 9789058230607), Conceptual Advances in Brain Research, R Miller (ed), Harwood Academic Publishers, pp. 53-96.
  • Nowak LG, Munk MHJ, James AC, Girard P, and Bullier J (1999) Cross correlation study of the temporal interactions between areas V1 and V2 of the macaque monkey. Journal of Neurophysiology 81, 1057-1074. doi: 10.1152/jn.1999.81.3.1057.
  • Nowak LG, Sanchez-Vives MV, and McCormick DA (1997) Influence of low and high frequency fluctuations on spike timing in visual cortical neurons. Cerebral Cortex 7, 487-501. doi: 10.1093/cercor/7.6.487.
  • Nowak LG, Munk MHJ, James AC, Nelson JI and Bullier J (1995) The structural basis of cortical synchronization. I. 3 types of interhemispheric coupling. Journal of Neurophysiology 74, 2379-2400. doi: 10.1152/jn.1995.74.6.2379.
  • Munk MHJ, Nowak LG, Nelson JI and Bullier J (1995) The structural basis of cortical synchronization. II. Localization of the common input. Journal of Neurophysiology 74, 2401-2414. doi: 10.1152/jn.1995.74.6.2401.
Neuronal elements activated by electrical stimulation and spread of stimulating current in the cortical gray matter
  • Nowak LG and Bullier J (1998) Axons, but not cell bodies, are activated by electrical stimulation in the cortical gray matter. I. Evidence from chronaxie measurements. Experimental Brain Research 118, 477-488. doi: 10.1007/s002210050304.
  • Nowak LG and Bullier J (1998) Axons, but not cell bodies, are activated by electrical stimulation in the cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segment. Experimental Brain Research 118, 489-500. doi: 10.1007/s002210050305.
  • Nowak LG and Bullier J (1996) Spread of stimulating current in the cortical grey matter of rat visual cortex studied on a new in vitro slice preparation. Journal of Neuroscience Methods 67, 237-248. doi: 10.1016/0165-0270(96)00065-9.
Corticocortical connections in vitro
  • Nowak LG, James AC and Bullier J (1997) Corticocortical connections between visual areas 17 and 18a of the rat studied in vitro : spatial and temporal organization of functional synaptic inputs. Experimental Brain Research 117, 219-241. doi: 10.1007/s002210050218.
MAIN PARTNERS in CerCo

Team DYNAMO, obviously : Emmanuel Barbeau, Leila Reddy, Jonathan Curot

Team PresAge : Caroline Fonta

Team SLAM : Céline Cappe

CURRENT COLLABORATIONS

Ali Maziz & Christian Bergaud, LAAS-CNRS, UPR 8001, Toulouse.

Lionel Dahan, CRCA, UMR 5169, Toulouse, France.

Véronique Gilard & Stéphane Balayssac, IMRCP, UMR 5623, Toulouse, France.

David Magne & Anne Briolay, ICBMS, UMR 5246, Lyon

TEACHING

Master of Neuroscience, Université de Toulouse.