The processing of sensory information is a fundamental operation of neurons within the brain. Each neuron receives hundreds of weighted synaptic inputs from other neurons, which it must process in order to evoke a functionally relevant output. The synaptic inputs to any given neuron are modifiable and activity-dependent changes in synaptic efficacy are thought to underpin network development, leaning and memory, learning and behaviour. Although we are beginning to understand the rules that govern synaptic integration and plasticity in vitro, little is known about how neurons encode sensory information or how experience-dependent changes in synaptic efficacy relate to learning and behaviour.
Our group is interested in understanding the cellular mechanisms involved in synaptic integration and experience-dependent plasticity in the cerebellum. By taking advantage of recent advances in in vivo intracellular recording techniques, our research focuses on three main areas.
To understand how sensory information is encoded in the intact brain, it is essential to determine the patterns of synaptic activity evoked during sensory experience and the integrative properties of individual neurons. Although single unit recordings in vivo have provided a basic understanding of sensory responses in single neurons, these experiments lack detailed information regarding subthreshold synaptic activity, spatial patterns of synaptic input, and the subcellular mechanisms involved in synaptic integration.
We use a multidisciplinary approach combining in vivo whole-cell electrophysiology, molecular and genetic manipulation of neural activity and neuronal tracing, to investigate the molecular mechanisms involved in synaptic integration in individual cerebellar neurons.
A central theory in modern neuroscience is that modifications in synaptic strength underpin learning, memory and behaviour. Activity-dependent changes in synaptic efficacy can proceed via a variety of signalling pathways that impact on the presynaptic release machinery or postsynaptic receptors mediating the response.
Our research focuses on identifying the extent to which pre- and postsynaptic ionotropic glutamate receptors are activated during sensory experience and what role they play during experience-dependent synaptic plasticity in the cerebellum. By exploiting a number of in vivo recording techniques, conditional gene knockout strategies and compartmental modelling we are exploring the impact of glutamate receptor-dependent synaptic plasticity in molecular layer interneurons both at the single cell and network level.
Inhibitory microcircuits play a key role in regulating neuronal excitability in the intact brain and understanding their function has been a primary goal for neuroscientists for several decades.
We use a multi-level approach combining in vivo electrophysiology, conditional gene knockout strategies and quantitative behavioural paradigms to investigate the extent to which cerebellar inhibitory microcircuits are modified by sensory experience and their role during cerebellar-dependent learning in awake behaving mice.
Mathy A., Ho SS., Davie JT., Duguid IC., Clark BA., Häusser M. (2009) Encoding of oscillations by axonal bursts in inferior olive neurons. Neuron., 62 (3): 388-99.
Duguid IC., Smart TG. (2008) Presynaptic NMDA receptors. In: Biology of the NMDA receptor - Frontiers in Neuroscience Taylor & Francis CRC press: 311-21.
Rancz EA., Ishikawa T., Duguid IC., Chadderton P., Mahon S., Häusser M. (2007) High-fidelity transmission of sensory information by single cerebellar mossy fibre boutons. Nature, 450 (7173) : 1245-8.
Duguid IC., Pankratov Y., Moss GW., Smart TG .(2007) Somatodendritic release of glutamate regulates synaptic inhibition in cerebellar Purkinje cells via autocrine mGluR1 activation. J. Neurosci., 27 (46) : 12464-74.