Sharott Group

sharott

Circuit mechanisms of dysfunction and development of therapy for movement 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 and basal ganglia circuits in vivo, both at the level of single neurons and of populations of neurons recorded across different nodes of the network. To gain insights in to the role of specific types of cell, we record and label neurons, allowing their molecular identity to be revealed and structural properties analysed.

To understand the working of basal ganglia 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 and basal ganglia neurons generate network activities and examine the effects of perturbing different circuit components using electrical and pharmacological 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 closed-loop deep brain stimulation in animal models of Parkinson’s disease.
  • Neuronal diversity and the role of interneurons in striatal microcircuits.
Selected Publications
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.
Sharott A
Gulberti A
Zittel S
Tudor Jones AA
Fickel U
Münchau A
Köppen JA
Gerloff C
Westphal M
Buhmann C
Hamel W
Engel AK
Moll CK

2014.J. Neurosci., 34(18):6273-85.

Sharott A
Grosse P
Kühn AA
Salih F
Engel AK
Kupsch A
Schneider GH
Krauss JK
Brown P

2008.Brain, 131(Pt 2):473-84.