Magill Group

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Some of the basal ganglia nuclei with their partner circuits in the thalamus and cerebral cortex.

Our overall goal is to provide detailed explanations of how brain circuit organisation supports normal and impaired behaviours. Focusing on a brain region called the basal ganglia, we monitor and manipulate different types of nerve cell to provide new insights into how their host networks operate. In taking advantage of the new understanding gained, we use specialised nerve cell types as entry points for novel therapeutic interventions that are designed to correct the brain circuit disorganisation and behavioural difficulties that arise in disease.

GPe neurons: structure is function

GPe neurons: structure is function

The molecular building blocks of cellular diversity in the external globus pallidus: All types of GPe neuron are revealed with immunoreactivity for HuCD (green). Arkypallidal neurons are revealed with FoxP2 (light blue), whereas prototypic GPe neurons express Nkx2-1 (red) and often PV (yellow).

The molecular building blocks of cellular diversity in the external globus pallidus: All types of GPe neuron are revealed with immunoreactivity for HuCD (green). Arkypallidal neurons are revealed with FoxP2 (light blue), whereas prototypic GPe neurons express Nkx2-1 (red) and often PV (yellow).

Reaching out: Arkypallidal neurons innervate the striatum and form synapses with spiny projection neurons.  Single axon terminal of an arkypallidal neuron (pseudocoloured red) forming a Type II synapse (arrow) with the dendritic shaft of a spiny projection neuron (green). The spine head of the same target neuron is forming a Type I synapse (arrow heads) with an axon terminal of a different type of cell (yellow).

Reaching out: Arkypallidal neurons innervate the striatum and form synapses with spiny projection neurons. Single axon terminal of an arkypallidal neuron (pseudocoloured red) forming a Type II synapse (arrow) with the dendritic shaft of a spiny projection neuron (green). The spine head of the same target neuron is forming a Type I synapse (arrow heads) with an axon terminal of a different type of cell (yellow).

Not all GPe neurons are created equal.

Not all GPe neurons are created equal.

Odd one out: neurons of the parafascicular nucleus (an example in blue) are not built like their thalamic neighbours (an example in red).

Odd one out: neurons of the parafascicular nucleus (an example in blue) are not built like their thalamic neighbours (an example in red).

The thalamus divided.

The thalamus divided.

Supercomputer modelling of basal ganglia circuit dynamics.

Supercomputer modelling of basal ganglia circuit dynamics.

A foundation for striatal function: a spiny projection neuron.

A foundation for striatal function: a spiny projection neuron.

‘Bad’ brain waves in Parkinsonism.

‘Bad’ brain waves in Parkinsonism.

The dichotomy in striatum revealed: Two different types of spiny projection neuron.

The dichotomy in striatum revealed: Two different types of spiny projection neuron.

Group Science

We recognise that the burden of disease is not borne evenly across all cell types in the brain.  It is thus imperative that the design of new strategies for treating disease symptoms is tempered by a mature knowledge of how different cell types fulfil their specialised roles to govern behaviour.  The overarching goal of our Programme is to fill this knowledge gap by delivering high-resolution readouts and mechanistic explanations of brain 'motor circuit' organization in the context of normal behaviours as well as impaired behaviours.  Focusing on basal ganglia and thalamocortical circuits, we harness cutting-edge technologies for identifying, monitoring, accessing and manipulating neurons in vivo to provide fundamental new insights into the specific cellular substrates of the neuronal network dynamics therein.  We place special emphasis on defining how the interactions and activities of identified cell types in these brain circuits vary according to the temporal profile of dopamine release and movement.  As a key corollary of this, we define how a paucity of dopamine release, as occurs in Parkinson’s disease and its animal models, impacts on the neuronal encoding of behaviour in these motor circuits.  In capitalising on the new level of understanding of the dynamics of identified neurons that is gained here, we also endeavour to exploit specified cell types and other circuit elements as novel points of entry for spatiotemporally-patterned interventions designed to not only dissect circuit function but also to correct circuit dysfunction and related behavioural deficits in Parkinsonism and other disorders of movement and memory.

We couple novel and advanced analytical techniques with experimental interventions that probe causal interactions between specified circuit elements with high spatiotemporal precision.  Our experiments centre on the use of wild type and genetically-altered rodents with intact or comprised midbrain dopaminergic systems, the readouts from which straddle multiple levels of function including molecular/genetic, structural, electrophysiological and behavioural.

Key Research Areas
  • Mechanisms underlying neuronal network activity in basal ganglia-thalamocortical circuits.
  • Cell-type-specific encoding of behaviour in basal ganglia-thalamocortical circuits.
  • Experimental models of movement/memory disorders involving basal ganglia-thalamocortical circuits.
  • Generation, dissemination and impact of aberrant neuronal oscillations in the Parkinsonian brain.
  • Cell-type-specific interventions for symptom relief in disease.
Longer-term Perspectives

Our research is designed to provide significant advances in the understanding of how specialised cell types in the basal ganglia work together with neurons in their partner brain circuits to control behaviour, for better or worse. We recognise that new understanding is critically important for building a stronger foundation from which to develop new therapeutic interventions in disease. We thus strive to progress from delivering new mechanistic insights, through generation of firm rationale to proof-of-concept studies that can be taken forward to inform and advance the future development of improved, personalised therapies.

Research Techniques
  • Electrophysiology (in vivo and in vitro)
  • Single-cell recording/labelling in vivo
  • Light and electron microscopy
  • Genetics-based approaches for cell monitoring and manipulation
  • Quantification of voluntary behaviours
  • Fast-scan cyclic voltammetry
Selected Publications
Unit Publication
Sharott A
Vinciati F
Nakamura KC
Magill PJ
2017.J. Neurosci., 37(41):9977-9998.
Unit Publication
Dodson PD
Dreyer JK
Jennings K
Syed EC
Wade-Martins R
Cragg SJ
Bolam JP
Magill PJ

2016.Proc. Natl. Acad. Sci. U.S.A., 113(15):E2180-8.

Unit Publication
Garas FN
Shah RS
Kormann E
Doig NM
Vinciati F
Nakamura KC
Dorst MC
Smith Y
Magill PJ
Sharott A
2016. Elife;5:e16088.
Unit Publication
Dodson PD
Larvin JT
Duffell JM
Garas FN
Doig NM
Kessaris N
Duguid IC
Bogacz R
Butt SJ
Magill PJ

2015.Neuron, 86(2):501-13.

Unit Publication
Abdi A
Mallet N
Mohamed FY
Sharott A
Dodson PD
Nakamura KC
Suri S
Avery SV
Larvin JT
Garas FN
Garas SN
Vinciati F
Morin S
Bezard E
Baufreton J
Magill PJ
2015.J. Neurosci., 35(17):6667-88.