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Dr Maria Usowicz

Neuronal function in the cerebellum; Down's syndrome

1. Voltage-gated calcium channels in the brain

P-type calcium channels were first described in the cerebellar Purkinje cell, but are thought to be widely distributed throughout the brain and to control many diverse fundamental processes. Mutations in the CACNA1A gene that encodes the main subunit (Cav2.1, alpha 1A) may underly various neurological disorders, such as different forms of migraine and ataxia.  We are investigating how the functional and molecular properties of P-type channels vary between different types of brain neurons and during neuronal maturation.

Purkinje cell 2

patch-clamp recording from a Purkinje cell in a slice of cerebellum during drug application from a macropipette

Patch-clamp recording from a Purkinje cell in a slice of cerebellum during drug application from a macropipette (right).

 

2. Synaptic transmission in the brain

In the brain, communication between cells occurs via the release of neurotransmitters at synapses. Our interests lie in the speed of transmission and how this is defined at a particular synapse, the quantal properties, the spatial spread of transmitter, and how these properties change during maturation of the brain. Currently our focus is on synaptic transmission at identified synapses (mossy fibre-granule cell, Golgi cell-granule cell) in immature and mature cerebellum.

3.  Down's syndrome

The cerebellum is essential for the coordination of movements. Motor deficits of varying severity are common to individuals with Down's syndrome (trisomy 21), such as slower development of and difficulty in acquiring new motor skills, strabismus (squint), nystagmus (oscillating eye movements), impaired speech, and altered posture, gait and balance.   In Down’s syndrome, there is loss of ~25% of granule neurons in the cerebellum. We are exploring how the intrinsic and synaptic properties of the surviving granule cells are altered in the Ts65Dn model.

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Research keywords

  • cerebellar slices
  • patch-clamp recording
  • tonic neurotransmission
  • cerebellar Purkinje cells
  • cerebellar granule cells
  • tonic inhibition
  • alternative splicing

Diseases related to this field of research

  • Down's syndrome
  • Down syndrome

Processes and functions relevant to this work

  • ageing
  • cell-specific expression of splice variants
  • splice variants and functional diversity

Equipment relevant to this work

  • Electrode puller
  • patch-clamp rig
  • thermal cyclers

Research findings

Figure 1. Harvesting of a cerebellar granule cell prior to RT-qPCR.  

Harvesting of a cerebellar granule cell prior to RT-qPCR.

 

Patch-clamp recording from a Purkinje cell in a slice of cerebellum during drug application from a macropipette

Patch-clamp recording from a Purkinje cell in a slice of cerebellum during drug application from a macropipette

 

 

Collaborations

  • Drosophila and Down's Syndrome: Dr James Hodge (Physiology and Pharmacology University of Bristol)
  • Purkinje cells and stem cells: Dr Kevin Kemp and Dr Alastair Wilkins (School of Clinical Sciences University of Bristol)
  • Purkinje cells in ageing: Prof. Richard Apps; Dr Nina Balthasar (Physiology and Pharmacology University of Bristol) and Dr Jon Brown (Clinical Medicine University of Exeter)