Review
Neurosciences
Werner Kilb
Summary: This article discusses the effect of GABA on neuronal excitability, the complex spatiotemporal interaction between GABAergic and glutamatergic inputs, and mechanisms influencing [Cl-](i) beyond Cl- transporters expression. Research suggests that during early developmental stages, GABA can act as an inhibitory neurotransmitter.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Juergen Graf, Chuanqiang Zhang, Stephan Lawrence Marguet, Tanja Herrmann, Tom Flossmann, Robin Hinsch, Vahid Rahmati, Madlen Guenther, Christiane Frahm, Anja Urbach, Ricardo Melo Neves, Otto W. Witte, Stefan J. Kiebel, Dirk Isbrandt, Christian A. Huebner, Knut Holthoff, Knut Kirmse
Summary: NKCC1 is the primary transporter for chloride uptake in immature principal neurons, and its function in vivo network dynamics and cognitive abilities remains unclear. The study found that deletion of NKCC1 from telencephalic glutamatergic neurons impacts neuronal synchrony in neonatal hippocampal brain slices, but has minor effects on network activity and behavioral performance in the long term.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Yasmine Belaidouni, Diabe Diabira, Jinwei Zhang, Jean-Charles Graziano, Francesca Bader, Aurelie Montheil, Clement Menuet, Gary A. Wayman, Jean-Luc Gaiarsa
Summary: The study found that in late symptomatic stages, there was no difference in the relative amount of KCC2 and NKCC1 in the hippocampus of Mecp2-null mice, but there was over-phosphorylation. There were also no differences in the inhibitory strength and reversal potential of GABA(A)-receptor-mediated responses in Mecp2-null CA3 pyramidal neurons compared to wild-type at any stages studied. These data indicate the presence of a functional chloride extrusion mechanism in Mecp2-null CA3 pyramidal neurons at symptomatic stages.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Marie Johne, Christopher Kaeufer, Kerstin Roemermann, Bjoern Gailus, Birthe Gericke, Wolfgang Loescher
Summary: Bumetanide failed to enhance the inhibitory effect of phenobarbital on neonatal seizures, but the combination of DIMAEB and bumepamine showed promising results in suppressing seizures, indicating potential for further development as more effective lead compounds for clinical trials.
Review
Neurosciences
Sam A. Booker, David J. A. Wyllie
Summary: NMDARs are essential for synaptic information transfer and plasticity in the majority of brain circuits. Inhibitory GABAergic interneurons exhibit diverse NMDAR expression and function, controlling cellular excitation in a synapse-specific manner. Further research is needed to fully understand the role of NMDARs in modulating GABAergic synaptic and circuit function.
Review
Clinical Neurology
Eline J. H. van van Hugte, Dirk Schubert, Nael Nadif Kasri
Summary: Epilepsy is a common neurological disorder associated with alterations in excitatory/inhibitory balance. While previous studies focused on reduced inhibition or increased excitation as the cause of epilepsy, recent research suggests that depolarizing gamma-aminobutyric acid (GABA) also contributes to epileptogenesis. During brain development, GABA switches from depolarizing to hyperpolarizing, and alterations in the timing of this transition are associated with neurodevelopmental disorders and epilepsy. This article discusses the role of depolarizing GABA in altered excitatory/inhibitory balance and seizure generation, highlighting it as a common factor in neurodevelopmental disorders and epilepsy.
Article
Biochemistry & Molecular Biology
Grzegorz Wiera, Katarzyna Lebida, Anna Maria Lech, Patrycja Brzdak, Inge Van Hove, Lies De Groef, Lieve Moons, Enrica Maria Petrini, Andrea Barberis, Jerzy W. Mozrzymas
Summary: This study demonstrates that MMP3 plays a key role in iLTP mechanisms, affecting behaviors that in part depend on GABAergic plasticity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Behavioral Sciences
Carlijn Peerboom, Corette J. Wierenga
Summary: The transition from depolarizing to hyperpolarizing GABA signaling during postnatal development is crucial for brain function and associated with neurodevelopmental disorders. Each developmental shift in GABA function regulates different aspects of neuron development, ensuring alignment with the developing network environment. Proper timing of the postnatal GABA shift may be influenced by sensory input and a developmental perspective is needed to understand the consequences of mismatches in connectivity, activity, and GABA signaling during brain development.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Neurosciences
Veronica Bonalume, Lucia Caffino, Luca F. Castelnovo, Alessandro Faroni, Sheng Liu, Jing Hu, Marco Milanese, Giambattista Bonanno, Kyra Sohns, Tal Hoffmann, Roberto De Col, Martin Schmelz, Fabio Fumagalli, Valerio Magnaghi, Richard Carr
Summary: The study shows that GABA depolarizes sural nerve axons and increases the electrical excitability of C-fibres via GABA(A) receptor. NKCC1 plays a role in maintaining intra-axonal chloride to stabilize C-fibre excitability. Activation of GABA(A) receptor can stabilize C-fibre excitability during sustained firing.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Neurosciences
Philip Hampel, Marie Johne, Bjoern Gailus, Alexandra Vogel, Alina Schidlitzki, Birthe Gericke, Kathrin Toellner, Wiebke Theilmann, Christopher Kaeufer, Kerstin Roemermann, Kai Kaila, Wolfgang Loescher
Summary: The study investigated the effects of NKCC1 expression on seizures and epilepsy using KO and WT mice. Results showed that while NKCC1 deficiency did not affect the induction and progression of epilepsy, it led to a more severe epileptic phenotype.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Maithe Loisy, Guillaume Bouisset, Sebastien Lopez, Maud Muller, Alena Spitsyn, Jeanne Duval, Rebecca Ann Piskorowski, Laure Verret, Vivien Chevaleyre
Summary: This study reveals a novel inhibitory plasticity mediated by cannabinoid type 1 receptor activation (CB1R-iLTD) in the CA2 region of the hippocampus, which plays a crucial role in social memory formation. The study also demonstrates that the previous induction of Delta-opioid receptor-mediated long-term depression (DOR-iLTDs) is necessary for the CB1R-iLTD to occur. The findings provide insights into the interplay between inhibitory plasticities and a new mechanism for social memory formation.
Article
Biotechnology & Applied Microbiology
Martina Parrini, Shovan Naskar, Micol Alberti, Ilaria Colombi, Giovanni Morelli, Anna Rocchi, Marina Nanni, Federica Piccardi, Severine Charles, Giuseppe Ronzitti, Federico Mingozzi, Andrea Contestabile, Laura Cancedda
Summary: Reducing NKCC1 expression by RNA interference restores intracellular chloride concentration and GABA-mediated inhibition in the Ts65Dn mouse model of Down syndrome, leading to improvement in neuronal network dynamics, while AAV-mediated NKCC1 knockdown rescues cognitive deficits in diverse behavioral tasks in these animals. These results establish a mechanistic link between NKCC1 expression and behavioral abnormalities in DS mice, providing a molecular target for new therapeutic approaches such as gene therapy.
Article
Neurosciences
Sana Al Awabdh, Florian Donneger, Marie Goutierre, Martial Seveno, Oana Vigy, Pauline Weinzettl, Marion Russeau, Imane Moutkine, Sabine Levi, Philippe Marin, Jean Christophe Poncer
Summary: KCC2, a neuron-specific chloride extruder, regulates the strength and polarity of GABAA receptor-mediated transmission and also plays a role in spinogenesis and excitatory synaptic function. The study identifies gephyrin as a novel anchoring molecule for KCC2 that stabilizes its plasma membrane expression and promotes its clustering near GABAergic synapses.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Maria Sancho-Alonso, Raquel Garcia-Garcia, Vicent Teruel-Marti, Marta Llansola, Vicente Felipo
Summary: This study found that chronic hyperammonemia enhances the function of GABA(A) receptors in the hippocampus and promotes the transmission of GABA neurotransmitters by reducing the membrane expression of GABA transporters and increasing the membrane expression of GABA(A) receptor subunits. Increasing extracellular cGMP can reverse this increase in function. The results of this study suggest that modulating GABA regulation may improve cognitive function in patients with hyperammonemia and hepatic encephalopathy.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Viktoria S. Pendeliuk, Igor V. Melnick
Summary: Synchronization of hippocampal interneurons (INs) relies on local cell interactions and intensity of network activity. In baseline conditions, a significant portion of inhibitory postsynaptic currents coincided between cells. Network activity induced excitatory and inhibitory events, with excitatory events capable of synchronizing IN firing. Glutamatergic mechanisms play a crucial role in initiating and dominating IN synchronization.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Guzel Valeeva, Sona Janackova, Azat Nasretdinov, Veronika Rychkova, Roman Makarov, Gregory L. Holmes, Roustem Khazipov, Pierre-Pascal Lenck-Santini
Article
Neurosciences
Guzel Valeeva, Azat Nasretdinov, Veronika Rychkova, Roustem Khazipov
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Article
Neurosciences
Gulshat Burkhanova, Kseniya Chernova, Roustem Khazipov, Maxim Sheroziya
FRONTIERS IN SYSTEMS NEUROSCIENCE
(2020)
Review
Physiology
Rosa Cossart, Roustem Khazipov
Summary: This review focuses on the development and self-organized dynamics of hippocampal circuits, exploring their role in learning and memory. It is found that the development of hippocampal cells and circuits starts during embryonic neurogenesis, and later experiences are integrated onto this framework. The article reviews the development of hippocampal cells and circuits at anatomical and functional levels, and describes the emergence of network dynamics in the hippocampus. Finally, open questions are posed in the article.
PHYSIOLOGICAL REVIEWS
(2022)
Article
Multidisciplinary Sciences
Roman Makarov, Mikhail Sintsov, Guzel Valeeva, Pavel Starikov, Dmitriy Negrov, Roustem Khazipov
Summary: Rats are born deaf but begin to hear at the end of the second postnatal week, when low-intensity sounds start to elicit responses in the auditory cortex as the ear canals open. Bone-conducted sounds evoke biphasic responses in the auditory cortex starting from postnatal day 8, indicating early integrity of the auditory system before the onset of low-threshold hearing.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Azat Nasretdinov, Alexander Evstifeev, Daria Vinokurova, Gulshat Burkhanova-Zakirova, Kseniya Chernova, Zoya Churina, Roustem Khazipov
Summary: This study introduces a novel digital inverse filter for accurate and efficient reconstruction of brain electrical signals. By adapting the inverse filter coefficients evaluation procedure for each recording channel, errors caused by deviations of the real values of RRC filter elements from their nominal values can be minimized.
Article
Endocrinology & Metabolism
Daria Vinokurova, Andrey Zakharov, Kseniya Chernova, Gulshat Burkhanova-Zakirova, Viktor Horst, Coline L. Lemale, Jens P. Dreier, Roustem Khazipov
Summary: The study investigates the development of ischemic lesions in the cortical depths using direct current coupled recordings in the rat barrel cortex. The results show that the lesions progress from the surface to the cortical depth and early changes in electrical activity can predict the severity of damage.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Neurosciences
Alina Vazetdinova, Fliza Valiullina-Rakhmatullina, Andrei Rozov, Alexander Evstifeev, Roustem Khazipov, Azat Nasretdinov
Summary: Cell-attached current-clamp recordings can measure resting membrane potential and synaptic/agonist responses in neurons, but may cause signal distortion.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Azat Gainutdinov, Dmitrii Shipkov, Mikhail Sintsov, Lorenzo Fabrizi, Azat Nasretdinov, Roustem Khazipov, Guzel Valeeva
Summary: In this study, scientists observed that somatosensory stimulation in newborn rats can evoke similar electrical activity as spontaneous early sharp waves (eSPWs), suggesting that sensory feedback from movements is involved in the association of eSPWs with myoclonic movements in neonatal rats.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Bulat Mingazov, Daria Vinokurova, Andrei Zakharov, Roustem Khazipov
Summary: Brain ischemia leads to slow voltage shifts in the cerebral cortex, including spreading depolarization (SD) and negative ultraslow potentials (NUPs), which are markers of brain injury. Different electrode materials and locations result in varying SD and NUP features. This study compared terminal cortical events during isoflurane or sevoflurane euthanasia using iridium and Ag/AgCl-based electrodes in the rat somatosensory cortex. The findings suggest that Ag and Ir electrodes can reliably assess early manifestations of terminal brain injury, but the late phase of NUP, which is present only on Ir electrodes, may be related to a yet unidentified factor associated with brain death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Aleksey V. Zaitsev, Roustem Khazipov
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Maxim Sheroziya, Roustem Khazipov
Summary: During the critical period of postnatal development, the brain is highly sensitive to external stimuli. In newborn rodents, the interaction between strong excitatory and inhibitory synapses and weak intrinsic currents in the thalamocortical system contributes to sensory-evoked early gamma oscillations and spindle bursts.
Article
Multidisciplinary Sciences
Elvira Juzekaeva, Azat Gainutdinov, Marat Mukhtarov, Roustem Khazipov
SCIENTIFIC REPORTS
(2020)
Article
Neurosciences
G. Valeeva, V Rychkova, D. Vinokurova, A. Nasretdinov, R. Khazipov
ZHURNAL VYSSHEI NERVNOI DEYATELNOSTI IMENI I P PAVLOVA
(2020)