Quick Project Snapshot
The modulation of sensory perception by the prefrontal cortex.
The brain has many areas specialised for specific functions, which must communicate with one another to generate an internal representation of our surrounding environment. It is therefore not surprising that disruptions to brain connectivity are the basis of many neuropathological diseases.
The prefrontal cortex exerts ‘top-down’ control of many cortical areas during complex emotional and cognitive behavior. This modulatory information courses through the upper layers of the cortex and synapses onto pyramidal neuron dendrites within the superficial cortical layers. Therefore, understanding prefrontal communication requires detailed knowledge of how cortical dendrites process this top-down information.
This project will combine multiple state-of-the-art techniques including two-photon microscopy, patch-clamp electrophysiology and optogenetics (light to control neurons) in vivo to probe the influence of the prefrontal cortex on sensory perception.
Specifically, the influence of prefrontal cortex communication on the activity of pyramidal neurons within the somatosensory cortex will be investigated during non-noxious sensory stimulation. The distal dendrites of cortical pyramidal neurons generate large NMDA-dependent voltage events, termed NMDA spikes, in response to sensory stimulation. The generation of these NMDA spikes are extremely important in neuronal response to sensory input and therefore whether prefrontal cortical activity modulates their generation and leads to changes in sensory perception will be investigated.
The results of this study will reveal the cellular mechanisms underlying prefrontal cortex control of other brain regions and will therefore shed light on diseases involving prefrontal cortical dysfunction.
Neural Networks Laboratory
Neurons are the building blocks of behaviour
Our goal is to understand the neural activity contributing to perception and behaviour in the mammalian brain. Individual neurons are continuously bombarded with thousands of synaptic inputs which must integrate to generate an internal representation of the external environment. We investigate how the brain processes this sensory information by measuring the activity of neurons within the neocortex in vivo using a variety of techniques including two photon calcium imaging, somatic and dendritic patch-clamp recordings and optogenetics.
We are particularly interested in the activity of dendrites, which are the thin neural processes that receive the vast majority of the neuron’s synaptic input. Dendrites act as independent signalling units, integrating information according to complex computational rules. The dendritic integration of synaptic input, its modulation and influence on global brain function and behaviour is the focus on our research.
Through our work, we not only aim to reveal how sensory information is received, transformed and modulated in neurons, but also how this processing of synaptic input contributes to the overall neural network activity underlying behaviour.
Palmer, L.M., Shai, A.S., Reeve, J.E., Anderson, H.L., Paulsen, O., Larkum, M.E. 2014. NMDA spikes enhance action potential generation during sensory input. Nature Neuroscience. 17(3). 383-390
Palmer, L.M. 2014. Dendritic integration in pyramidal neurons during network activity and disease. Brain Re. Bull. 103. 2-10.
Palmer, L.M.*, Schulz, J.M.*, Larkum, M.E. 2013. Addendum article: Layer-specific regulation of cortical neurons by interhemispheric inhibition. Communicative & Integrative Biology. 6:3. e23545-1 - e23545-5.
Palmer, L.M., Schulz, J.M., Murphy, S.M., Ledergerber, D., Murayama, M, Larkum, M.E. 2012. The cellular basis of GABAB-mediated interhemispheric inhibition. Science. 335. 989-993
Palmer, L.M., Murayama, M, Larkum, M.E. 2012. Inhibitory regulation of dendritic activity in vivo. Frontiers in Neural Circuits. 6. 1-10
Granato, A., Palmer, L.M., De Giorgio, A., Tavian, D., and Larkum, M.E. 2012. Early exposure to alcohol leads to a permanent impairment of dendritic excitability in neocortical pyramidal neurons. J. Neurosci. 32(4): 1377-1382
Palmer, L.M., Clark BA, Gründemann J., Roth A., Stuart G.J., Häusser M. 2010. Initiation of simple and complex spikes in cerebellar Purkinje cells. J Physiol. 15(588): 1709-17
Palmer, L.M. and Stuart G.J. 2009. Membrane potential changes in dendritic spines during action potentials and synaptic input. J. Neurosci. 29(21): 6897-903
Stuart, G.J. and Palmer, L.M. 2006. Imaging membrane potential in dendrites and axons of single neurons. Pflugers Archiv. 543(3): 403-10
Palmer, L.M. and Stuart, G.J. 2006. Site of action potential initiation in layer 5 pyramidal neurons. J. Neurosci. 26(6): 1854-63.
Murphy, S.M., Palmer, L.M., Nyffeler, T., Müri, R., Larkum, M.E. 2016. Transcranial Magnetic Stimulation (TMS) inhibits cortical dendrites. eLife. 5:e13598, 1-12.
Mayrhofer, J.M., Haiss, F., Hänni, D., Weber, S., Barrett, M.J., Ferrari, K., Maechler, P., Saab, A., Stobart, J., Wyss, M.T., Zuend, M., Johannssen, H., Osswald, H., Palmer, L.M., Revol, V., Schuh, C., Urban, C., Hall, A., Innerhofer, E., Larkum, M.E., Zeilhofer, H.U., Ziegler, U., and Weber, B. 2015. Design and performance of an ultra-flexible two-photon microscope for in vivo research. Biomedical Optics Express. 6(11): 4228-37.
All Projects by this LabThe modulation of sensory perception by the prefrontal cortex.
The Florey's Epilepsy division is a world-leading centre for epilepsy research. The division has major groups at both the Florey’s Austin and Parkville campus. The group studies mechanisms that cause epilepsy from the level of cells to the function of the whole brain. We use technologies including advanced MRI and cutting edge cellular physiology techniques to allow us to understand genetic and acquired mechanisms that give rise to epilepsy. Together with our colleagues from The University of Melbourne and across Australia we are working towards finding a cure for epilepsy.