Dr David Parker

Neuronal networks

In order to understand how behaviours are generated we need to understand the networks underlying sensory, motor, and cognitive functions. Network activity reflects the molecular, cellular, and synaptic properties of its component neurons. We thus (at least) need to know the neurons that form a network, their connectivity, and their functional properties.

Network analyses are complicated by the large number of components that typically have to be studied, and the difficulties of directly relating cellular properties to behaviourally-relevant outputs. We use the locomotor network in the spinal cord of the lamprey, a model vertebrate system, to examine general principles of network function. This network generates alternating muscle activity on the left and right sides of the body. While the lamprey locomotor network is claimed and frequently cited as being characterised, in reality there are many areas of uncertainty, gaps that are ignored or assumed, and even examples of claimed experimental data that does not exist. These aspects need to be addressed before we can claim any degree of understanding. We combine electrophysiological, computational, molecular, and anatomical approaches to focus on several network aspects:

Activity-dependent plasticity of network synapses

Activity-dependent synaptic plasticity has been studied extensively, with a focus on long-term changes. We are examining the role of the short-term activity-dependent plasticity that develops during repetitive cycles of network activity at specific types of network synapses, and how the different forms of activity-dependent plasticity at different network synapse interact to influence the patterning of ongoing network outputs. This is done using experimental and computational approaches.

Cellular, synaptic, and network variability

Variability has traditionally been ignored in network analyses. It is now recognized that variability is an intrinsic component of nervous systems (and should be of any adaptive physiological system), that can influence cellular and synaptic function and plasticity, and thus network function. We are examining variability within identified neuronal and synaptic classes, and how this influences network outputs (which are also highly variable) and network plasticity.

Network plasticity

While a networks organisation and functional properties must generate reliable outputs, the output may need to rapidly change. This can be evoked by activity- or neuromodulator-dependent plasticity of cellular and synaptic properties. While these mechanisms can be studied independently, interactions can occur within and between these effects: synaptic activity or modulation can influence activity-dependent synaptic plasticity (“metaplasticity”); neuronal activity can influence neuromodulator release; and neuromodulators can interact (“metamodulation”). Cellular and synaptic properties are thus not simply plastic, but plasticity is both plastic and modulatory. The potential complexity or subtlety resulting from these interactions, which are likely to occur under natural conditions, is daunting. We are using the locomotor network to examine these interactive effects.

Network changes following functional recovery after spinal cord injury

The lamprey, and other lower vertebrates, recovers locomotor function after complete spinal cord lesions. Analyses of this effect have focused on the regrowth of axons across lesion sites. We are instead examining how network organisation and functional properties change above and below spinal cord lesion sites. We have identified a range of morphological and functional changes in the locomotor network, in sensory inputs, and in regenerated axons. There are also changes in neuromodulatory effects after lesioning, which suggest that pharmacological approaches to spinal cord injury cannot be based on an understanding of modulatory effects in the unlesioned spinal cord. We now need trying to relate the varied changes we have identified to the recovery of locomotor function.

Collaborators

Prof Vipin Srivastava, University of Hyderabad