Neuronal dendritic architecture in the LSN
Steven J. West
DPhil (Oxon.) BSc (Port)
Exploration of neuronal circuitry in health and disease
My research focuses on studying neuronal connectivity within the central nervous system, with the aim of understanding how neuronal circuitry processes information leading to the emergence of cognitive state and behaviour, and how these connections are altered in disease to produce maladaptive behavioural phenotypes.
My current focus is on the dorsal horn of the spinal cord, a key initial relay in the processing of somatosensory information, where peripheral somatosensory information undergoes important filtering and modulating via primed dorsal horn circuits from previous stimulation, and from descending cognitive information from higher CNS centres. Understanding the organisation of the circuitry of the dorsal horn will produce a better understanding of these important processes.
The dorsal horn is an important regulator of somatosensory processing, and it plays an important role in many diseases of the somatosensory nervous system. One important disease state is neuropathic pain, resulting from a lesion or disease to the somatosensory nervous system. Characterised by ongoing pain, hyperalgesia and allodynia, this condition is debilitating for patients and often has no adequate treatment. Following a lesion or other disease process to the peripheral nerve, the dorsal horn shows particular reactions which are believed to contribute to the neuropathic phenotype and also involve re-wiring of dorsal horn connections. Our research also focuses on understanding how the dorsal horn reacts to peripheral nerve lesions in order to understand how changes in the dorsal horn contribute to the neuropathic pain phenotype.
Sikandar S. et al, (2017), Physiol Rep, 5
Sleigh JN. et al, (2017), Proc Natl Acad Sci U S A, 114, E3324 - E3333
Maternal CASPR2 antibodies and neurodevelopmental disorders in the off spring: epidemiological findings and an animal model
Coutinho E. et al, (2017), LANCET, 389, 18 - 18
In order to study connectivity we use histological interrogation with high resolution confocal microscopy and a range of image processing and analysis techniques. We routinely use clearing methods to help generate large 3D datasets for analysis, and have developed an image processing and analysis platform for the unbiased and automated assessment of different components of the dorsal horn. This image processing and analysis suite (named StereoMate) allows the measurement of number, sizes and shapes of 3D objects, including synapses and neurons, within the dorsal horn in an automated manner, allowing the measurement of large numbers of objects (100,000s) in each study.
Using these tools, we are able to assess dorsal horn connectivity through assessment of neuronal & synaptic distributions, in order to understand its connectivity in health and disease.
Key Words: histology; immunofluorescence; confocal microscopy; tissue clearing; antigen retrieval; stereology; automated image processing; automated image analysis; StereoMate; connectivity; neuronal circuitry; dorsal horn; neuropathic pain