1. Organization of motor circuits.
2. Role of neuropeptides in synaptic and behavioural plasticity.
3. Synaptic, cellular and molecular mechanisms of learning and memory.
This work has been continuously funded by the BBSRC and MRC and various international bodies from 1969 until the present. Highlights include the 'MRC Neurophysiologyy Research Group' (1983-1988), SERC Rolling Programme grant in 'Arthropod and Molluscan Neuroscience' (1989-1991), EEC 'receptor club grants (1990-1996), BBSRC IRC in 'Simple nervous systems' (1991-1999). I led the successful bid for the IRC that made Sussex the major centre for Invertebrate Neuroscience in the UK.
My laboratory has been a major centre for post-graduate training and 29 students have graduated with a D.Phil. 14 graduate students and post-doctoral fellows have obtained academic positions at Universities in the UK and abroad.
Learning and memory
The main aim of our current research is to understand the fundamental behavioural, cellular and molecular mechanisms underlying memory formation in the brain using a multidisciplinary appoach that includes computational modelling. We use the snail, Lymnaea, as a model organism for these studies because molecular and electrical changes induced by learning can be studied at the level of individually identified giant neurons that play a key role in the learning circuit. Work on the 'simple' brains of invertebrates has provided a major stimulus for work on learning and memory in the neurosciences and a nobel prize was recently awarded for this type of research. In my laboratory, we are paricularly are interested in the temporal sequence of electrical and molecular events that lead to long-term memory traces. In the snail, as in all animals including man, different phases of memory (short, intermediate and finally long-term memory) have a sequence of temporal domaines that have different electrical and molecular and mechanisms. We recently discovered that increase in the intrinsic excitability of neurons and increases in the strength of synaptic connections between neurons form part of the long-term memory trace, whereas reductions in synaptic inhibition contribute to intermediate memory. Consolidation of long-term memory trace is dependent in the nitric oxide (NO)-GMP signalling pathway and a key finding is that the the level of mRNA from the nNOS (neural nitric oxide synthase) gene is upregulated by learning. This is due to a novel mechanism involving the downregulation of an antiNOS transcript that normally supresses NO production in naive snails (collaboration with Korneev and O'Shea).
Current BBSRC-funded research project, 2010-2013 (collaboration with O'Shea and Kemenes) 'Decision making and learning in neural networks'
How the nervous system makes decisions on what to do next from a repertoire of possible behaviors is one of the most important questions in neuroscience. Our knowledge of the detailed neural circuitry underlying a variety of reflexive and centrally generated behaviors in Lymnaea offers the exellent possibility of understanding the mechanisms involved. Behaviour is often initiated by sensory stimuli. For instance the taste of food initiates ingestion. Painful stimuli inhibit feeding but initiate avoidance responses. However, these responses are not necessarily automatic but are adaptive and modified by previous experience (learning). The detailed mechanisms (neural and molecular) underlying these adaptive reponses to sensory stimuli are of general interest and will be the major question to be asked in this project.
New BBSRC-funded research project, 2013-2016 (collaboration with Ildiko Kemenes and O'Shea) 'Lapses in memory: opportunities for adaptive behaviour'
Our aim in this project is to understand, at the level of defined neural networks, how lapses in memory operate as choice points providing flexibility in memory consolidation. Memory lapses are susceptible periods during consolidation which provide opportunities for behavioural adaptation. Our previous work showed that at periods of transition between memory phases memory recall is weakened, allowing novel sensory stimuli to block consolidation of long-term memory. We wish to test the generality of this finding and to investigate the neural and molecular mechanisms involved.