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Co-ordinated neuronal activity is intrinsically linked with behaviour and malfunction of neuronal coordination results in psychiatric and neurological disorders. Timing is crucial for neuronal integration including events lasting from milliseconds up to several seconds. Much of the neuronal activity is rhythmic in the brain, as rhythmicity facilitates local and global interactions and enables the representation of temporal sequences.

Rhythmicity provides flexibility by resetting the frequency, amplitude and phase of population activity for encoding and delivering information in support of behavioural needs. Importantly, firing of single and groups of neurons can change systematically relative to the population rhythm and reflect temporal coding of information.

One of the most studied and widespread cortical oscillations is rhythmic slow activity in the theta frequency range, typically 4-12 Hz in the temporal cortex of rodents. Theta oscillations modulate higher frequency gamma (30-120 Hz) oscillations associated with cognitive processes in both rodents and humans. Such cross-frequency coupling is a basic principle of brain function as changes in coupling strength indicate dynamic changes in neuronal network activity underlying behaviour, cognitive states such as navigation, decision-making and memory performance.

Key Research Areas: 

  • To define how specific cell types contribute to the timing of neuronal population activity in the CA3 area of the hippocampus.
  • To establish the identity of GABAergic neurons in the CA1 and CA3 areas and determine their in vivo firing patterns relative to theta, gamma and 100-200 Hz network oscillations and pyramidal cell activity.
  • To test the hypothesis that disinhibition, i.e. the phasic inhibition, or deactivation of key GABAergic neurons in the CA3 area is a condition of the synchronous pyramidal cell discharge in CA3 assembly activity that generates sharp waves in the CA1 area.
  • To explain how behaviour specific changes in interneuron firing contribute to pyramidal assembly activity.
  • To explain the role of identified neurons in well-defined and behaviourally significant cortical network events.

Longer-term Perspectives: 

We explore how distinct neuronal types contribute to behaviour, and how the network mechanisms governing neuronal activity relate to both normal and abnormal brain function. We hypothesise that temporal coordination of neuronal assemblies is regulated by a temporal redistribution of inhibition over principal cell subcellular domains.
We reveal how the firing patterns of different GABAergic, cholinergic and glutamatergic neurons relate to network oscillations during different behavioural states such as movement and sleep and how their connectivity to other cells can provide a mechanism for these underlying network oscillations.

Research Techniques: 

  • In vivo extracellular recordings from single neurons followed by juxtacellular labelling in drug-free freely moving rats and head-restrained mice during behaviour
  • Spike train analysis and coupling to local field potential oscillations for single cells and multi-unit activity
  • Investigation of synaptic mechanisms governing delta, theta, gamma, and ripple oscillations
  • Characterisation of identified hippocampal place cells
  • Cell type identification of recorded neurons from both the basal forebrain, hippocampal formation, and neocortex
  • Analysis of axonal arbours and their postsynaptic targets (GABAergic interneurons, GABAergic and cholinergic projection neurons, principle cells)
  • Mapping subcortical inputs to specific types of cortical interneuron with anterograde and retrograde tracers
  • Immunohistochemical characterisation and HRP-based diaminobenzidine processing of high-quality post-mortem human and rodent basal forebrain and cerebral cortical samples for light and electron microscopy
  • Investigation of synaptic mechanisms governing delta, theta, gamma, and ripple oscillations
  • Confocal and electron microscopic analysis of identified neural circuits, synapses and subcellular distribution of ion channels and receptors

Our team

GABAergic septo-hippocampal neuron

Reconstruction of a rhythmically bursting theta-coupled GABAergic rat medial septal neuron projecting to both the CA1 region of the hippocampus and the dorsal subiculum. Neuron D55c was recorded and labelled by Dr Damien Lapray and reconstructed by Mr Ben Micklem. This septo-hippocampal neuron synaptically targeted GABAergic neurons and showed a preference for bistratified GABAergic neurons in contrast to nNOS-expressing neurons in CA1. Reference: Unal G, Crump MG, Viney TJ, Éltes T, Katona L, Klausberger T, Somogyi P. Spatio-temporal specialization of GABAergic septo-hippocampal neurons for rhythmic network activity. Brain Structure and Function, 2018. doi: 10.1007/s00429-018-1626-0.

Related research themes