Sharott Group

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Sharrott

Circuit mechanisms of dysfunction and development of therapy for brain disorders

Abnormal co-ordination of neuronal activity in cortico-basal ganglia networks underlies several neurological and psychiatric disorders. In many cases, the loss or disruption of one neuronal population leads to widespread changes in function across the entire network. Our objective is to understand how these processes cause disease and to develop therapeutic interventions that restore network function and reduce symptoms.

Group Science

Our group examines function and dysfunction of cortical-basal ganglia-thalamic circuits in vivo, both at the level of single neurons and of populations of neurons recorded across different nodes of the network. To understand the working of forebrain circuits at the network level, we use high-density multi-electrode arrays that enable many neurons to be recorded from several structures simultaneously. We utilise both of these techniques to elucidate how cortical, basal ganglia and thalamic neurons generate network activities and examine the effects of perturbing different circuit components using electrical and optogenetic stimulation. By performing these experiments in the healthy brain and models of disease, these methods can be used to understand how co-ordinated network activity underlies the symptoms of disorders such as Parkinson’s disease and Obsessive Compulsive Disorder. Our ultimate aim is to use the insights from these experiments to develop closed-loop electrical stimulation strategies to treat these diseases.

Key Research Areas
  • Network mechanisms underlying pathological oscillations in Parkinson’s disease.
  • Development of novel closed-loop deep brain stimulation approaches for brain disorders.
  • The role of motor thalamo-cortical circuits in adaptive behaviour.
  • Neuronal diversity and the role of interneurons in striatal microcircuits.
Research Techniques
  • Analysis of intraoperative recordings from functional neurosurgery 
  • Closed-loop deep brain stimulation 
  • Multichannel electrophysiological recordings 
  • Cell-type selective optogenetics 
  • Transynaptic tracing
Selected Publications
Unit Publication
Cagnan H
Mallet N
Moll CK
Gulberti A
Holt AB
Westphal M
Gerloff C
Engel AK
Hamel W
Magill PJ
Brown P
Sharott A
2019. Proc. Natl. Acad. Sci. U.S.A., 116:16095-16104.
Unit Publication
Holt AB
Kormann E
Gulberti A
Pötter-Nerger M
McNamara CG
Cagnan H
Baaske MK
Little S
Köppen JA
Buhmann C
Westphal M
Gerloff C
Engel AK
Brown P
Hamel W
Moll CK
Sharott A
2019. J. Neurosci., 39(6):1119-1134.
Unit Publication
Sharott A
Vinciati F
Nakamura KC
Magill PJ
2017. J. Neurosci., 37(41):9977-9998.
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.
Doig NM
Magill PJ
Apicella P
Bolam JP
Sharott A
2014. J. Neurosci., 34(8):3101-17.
Datasets and resources

Like other Groups at the MRC BNDU, we are committed to best practice in open research.  We have created and curated a range of primary data, metadata and related resources that can be readily downloaded by external users from the MRC BNDU's Data Sharing Platform. We are part of the team that created CHAMBER, a novel chemoarchitectonic atlas of mouse thalamus and other brain regions.

Sharott A
Doig N
Garas F
Vinciati F
Magill PJ
10.5287/bodleian:VYqnPkxkb