The roles played by a ion channels, neurotransmitter receptors and a wide range of modulatory proteins forms a large part of the neuroscience research within the School of Physiology and Pharmacology. Investigations into the molecular mechanisms by which AMPA and NMDA receptor expression are controlled have been fundamental to our understanding of the physiological changes seen in neuronal plasticity while research into the mechanisms of action of Ca2+, Na+ and K+ channels have revealed how multiple ion fluxes control neuronal activity.
Neuronal plasticity is fundamental to learning and memory. Research covers a broad range of forms of plasticity in various cortical regions of the brain. Long-term potentiation (LTP) and long-term depression (LTD) are widely viewed as cellular substrates for memory mechanisms. Indeed NMDA receptor-dependent LTD has recently been shown to be the form of plasticity that underlies visual recognition memory in the perirhinal cortex. Metabotropic glutamate receptors, which were first discovered here at Bristol, play a major role in many different forms of both long- and short-term plasticity such as LTD and paired-pulse facilitation.
Research in this area is focused on determining the neural substrates of olfactory memory, visual recognition memory and spatial memory. All of these forms of memory provide excellent model systems with which to probe the cellular and molecular processes that underlie memory aquisition, consolidation and retrieval, as well as the neural networks involved in coordinating activity across mutiple brain regions.
Much of the work on neuronal sensory mechanisms centres on the detection and perception of noxious stimuli such as excess heat, cold and pain - nociception. For instance, recent work has shown that spinal noxious- and innocuous-cold circuits are differentially modulated (Leith et al 2010) and that mTOR may represent a novel therapuetic route for pharmacological intervention in persistent pain states (Géranton et al 2010). We also focus on how nociception and pain may be controlled both by endogenous neural mechanisms (Howorth et al 2009) and through the development of novel therapeutic approaches.
Movement is central to any behavioural response and the cerebellum is the largest motor control centre in the brain. Thus research into the the control of voluntary movements are focused on this structure, in particular the climbing fibre pathways linking the inferior olive to the cerebellum. Different zones within the cerebellum receive inputs from well defined regions of the inferior olive and project to specific vestibular and cerebellar nuclei. However, recent evidence suggests that individual modules do not necessarily have distinct functions in motor control (Cerminara and Apps 2010).
Neurodegenerative diseases and psychiatric conditions are a major national concern, with the number of people set to suffer cognitive impairments due to various forms of dementia set to rise significantly in the UK over the coming years with an aging population. Work into the mechanisms of dementias such as Alzheimer's Disease is therefore crucial to understanding how disease progression affects cognition. Work in the School, in association with industrial partners Pfizer, is investigating the role played by amyloid proteins in the disruption of neuronal plasticity and how that feeds into the disruption of memory.
Equally important are investigations into the role of the loss of synchronous neuronal activity in models of schizophrenia or ADHD that may lead to dysfunctional interactions between brain regions. Such disruption leads to impaired neural coordination that may be the basis for the sensory confusion and cognitive overload that lies at the heart of these conditions.
Cardiac disease is the biggest cause of mortality in the UK and hypertension is a major contributing factor to this. The School has extensive research projects into the control of blood pressure and obesity by the CNS, which are detailed in the Cardiovascular theme pages.