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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.

Brasenose College alumna:

  • Nicholas Kurti Junior Research Fellow in Neuroscience
  • DPhil in Neuroscience
  • MSc in Neuroscience

Collaborators

Dr Linda Katona

Senior Postdoctoral Neuroscientist

Cellular and Systems Neuroscience

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.

A novel hippocampal CA1-dentate gyrus back-projecting GABAergic neuron

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

Recent publications

More publications