Research groups
Keywords
hippocampus; GABAergic inhibition; interneurons; pyramidal cells; medial septum; GABAergic long-range projections; disinhibition; memory formation; network oscillations: theta, gamma, sharp wave-ripples; movement; sleep; rest; rapid-eye-movement sleep; in vivo neurophysiology; optogenetics; behaviour; neuroanatomy.
Websites
Colleges
Brasenose College alumna:
- Nicholas Kurti Junior Research Fellow in Neuroscience
- DPhil in Neuroscience
- MSc in Neuroscience
Collaborators
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Tim Viney
Career Development Fellow
Dr Linda Katona
Academic Visitor - Research Fellow, University College Cork
- HRB Emerging Investigator
- SFI-IRC Pathway Investigator
- BBRF NARSAD Young Investigator
Cellular & Systems Neuroscience and Host-Microbiome Research
Research
My research focuses on understanding the neuronal mechanisms underlying rhythmic neuronal activity and its roles in learning and memory formation.
Much of the activity in the brain is rhythmic resulting from the simultaneous activation of connected groups of neurons. Such coordinated neuronal activity reflects the coding of information in time and is linked with behaviour. Abnormal neuronal coordination and aberrant brain rhythmicity are common in neurological and neuropsychiatric disorders, including those affecting the memory centres e.g. Alzheimer's disease, epilepsy, schizophrenia etc. Thus, how does rhythmic neuronal activity relate to memory formation during normal and abnormal brain function?
One of the most studied and widespread brain rhythms are the 4-12 Hz theta oscillations. In the cerebral cortex, theta oscillations are present during movement, cognitive tasks and certain stages of sleep. I aim to define how theta generated in subcortical brain areas is implemented in the rodent cortex by different types of neuron. Specifically, I use combinatorial viral labelling strategies together with optogenetics and multi-unit electrophysiology in freely moving mice to investigate how distinct medial septal GABAergic neurons regulate the rhythmic disinhibition of hippocampal pyramidal cells during memory-guided behaviour.
Biography
I graduated from Sapientia Hungarian University of Transylvania, Romania, in 2009 with Ing. Dipl. in Computer Engineering. During my final year of engineering studies, I joined the group of Prof Peter Somogyi as a visiting undergraduate, where I developed quantitative, electron microscopy-constrained methods for the comparison of the dendritic arborisation and the total number of input synapses received by parvalbumin-expressing basket cells in the hippocampal CA2/3 area and CA1 (Tukker et al 2013 J Neurosci). In 2009, I completed an MSc in Neuroscience at the University of Oxford, which included one project examining pitch discrimination in freely moving ferrets (Oxford Auditory Neuroscience Group, Department of Physiology, Anatomy and Genetics) and a second project investigating the input and output synaptic organisation of axo-axonic cells in hippocampal CA2/3 recorded in vivo under urethane anaesthesia (Viney et al 2013 Nat Neurosci; Somogyi Group).
I conducted my DPhil studies under the joint supervision of Prof Peter Somogyi and Prof Thomas Klausberger (Medical University of Vienna, Associate Unit Member). In my project, I tested the hypothesis that differences in connectivity and molecular composition across different hippocampal interneuron types reflect the specialisation in their functions during movement and slow-wave sleep. I achieved this by recording the activity of distinct types of hippocampal GABAergic interneuron and demonstrated that these inhibit different subcellular pyramidal cell compartments at different times during network activity (Katona et al Neuron 2014; Viney et al Nat Neurosci 2013; Lapray et al Nat Neurosci 2012). This work contributed to the development, and provided evidence for, the concept that cyclical subcellular redistribution of inhibition underlies changes of excitability in hippocampal networks. I documented my observations in the doctoral thesis, entitled “The role of cell-type selective synaptic connections in rhythmic neuronal network activity in the hippocampus”. In recognition of this work, I was awarded the very prestigious Sieratzki UK-Israel 2017 UK Young Researcher’s Prize, FENS-Kavli Ph.D. Thesis Prize, BNA Postgraduate Award and The Physiological Society Pfizer Prize in Cellular and Integrative Neuroscience.
As a postdoctoral neuroscientist, I led two research projects to completion identifying the contribution of distinct long-range projecting hippocampal GABAergic cell types to regulating network activity in vivo (Katona et al 2017 Hippocampus; Katona et al 2020 Brain Struct Funct). These long-range inhibitory cells coordinate brain activity through rhythmically binding excitatory cells in the different brain areas into cooperative networks. Understanding of this is paramount as rhythmic brain activity is important in numerous aspects of brain function e.g. memory, cognition, attention and sleep. Central to the delivery of this research was my coaching and supervision of other staff and undergraduate and postgraduate project students.
Reconstruction of a novel somatostatin-expressing long-range GABAergic neuron back-projecting from the hippocampal CA1 region to the dentate gyrus (Katona et al 2017 Hippocampus). Neuron ZsB49b was recorded and labelled by Dr Zsolt Borhegyi and reconstructed by Mr Ben Micklem. The neuron ZsB49b which we have described in great depth does not resemble any previously published GABAergic neuron in its connections or activity. Based on the location of its axon terminals, it is likely to regulate dendritic integration of inputs from both the CA3 area and the entorhinal cortex while simultaneously assisting in the coordination between the CA1 area and the dentate gyrus, as evidenced by its strong excitation during sharp wave-ripples.
Techniques
- extracellular single neuron recording and juxtacellular labelling in awake rodents;
- high resolution structural analysis of the recorded cells, including molecular, light, confocal and electron microscopic definition of synaptic connections;
- extracellular multiple single-unit recording combined with optogenetics and chemogenetics;
- behavioural testing;
- combinatorial retrograde and anterograde viral tracing;
- analysis of spike timing and network oscillations;
- histology and immunohistochemistry;
- neuronal reconstruction;
Key publications
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Synaptic organisation and behaviour-dependent activity of mGluR8a-innervated GABAergic trilaminar cells projecting from the hippocampus to the subiculum.
Journal article
Katona L. et al, (2020), Brain Struct Funct
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Behavior-dependent activity patterns of GABAergic long-range projecting neurons in the rat hippocampus.
Journal article
Katona L. et al, (2017), Hippocampus, 27, 359 - 377
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Sleep and movement differentiates actions of two types of somatostatin-expressing GABAergic interneuron in rat hippocampus.
Journal article
Katona L. et al, (2014), Neuron, 82, 872 - 886
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Behavior-dependent specialization of identified hippocampal interneurons.
Journal article
Lapray D. et al, (2012), Nat Neurosci, 15, 1265 - 1271
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Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells in vivo.
Journal article
Viney TJ. et al, (2013), Nat Neurosci, 16, 1802 - 1811
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Distinct dendritic arborization and in vivo firing patterns of parvalbumin-expressing basket cells in the hippocampal area CA3.
Journal article
Tukker JJ. et al, (2013), J Neurosci, 33, 6809 - 6825
Recent publications
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Synaptic organisation and behaviour-dependent activity of mGluR8a-innervated GABAergic trilaminar cells projecting from the hippocampus to the subiculum.
Journal article
Katona L. et al, (2020), Brain Struct Funct
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GABAergic Medial Septal Neurons with Low-Rhythmic Firing Innervating the Dentate Gyrus and Hippocampal Area CA3.
Journal article
Salib M. et al, (2019), J Neurosci, 39, 4527 - 4549
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Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics.
Journal article
Harris KD. et al, (2018), PLoS Biol, 16
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Spatio-temporal specialization of GABAergic septo-hippocampal neurons for rhythmic network activity.
Journal article
Unal G. et al, (2018), Brain Struct Funct, 223, 2409 - 2432
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Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo.
Journal article
Lau PY-P. et al, (2017), Brain Struct Funct, 222, 1809 - 1827
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Behavior-dependent activity patterns of GABAergic long-range projecting neurons in the rat hippocampus.
Journal article
Katona L. et al, (2017), Hippocampus, 27, 359 - 377