A fundamental question in neuroscience is how neurons receive, process, and transmit signals, transforming sensory input to behavioral output. At the cellular level, most models of neuronal signaling focus on integration of synaptic potentials in the dendrites, soma, and axon initial segment, while the distal axon simply transmits action potentials with no further processing. However, growing evidence suggests that axons can also influence neuronal signaling. For example, myelination of axons, which primarily affects the rate of action potential propagation, can have profound impacts on behavior during postnatal development, and demyelinating diseases can lead to severe motor and cognitive impairments. More subtle changes in axonal properties, mediated by ligand-gated receptors, voltage-gated ion channels, or structural properties can also affect the fidelity, waveform, and amplitude of action potentials, leading to physiological and pathophysiological changes in synaptic transmission. We are interested in understanding how axonal plasticity participates in cellular computation and signal processing in neural circuits. In particular, we are interested in how short-term (milliseconds to seconds) changes mediated by activation of axonal receptors or inactivation of voltage-gated channels modify action potentials and synaptic transmission during ongoing activity; and how long-term (minutes to days) changes in axonal receptor/channel expression or bouton size/shape contributes to synaptic plasticity and behavioral learning and memory.
To answer these questions we currently study the axons of cerebellar granule cells which form the parallel fibers. These axons are particularly amenable to these experiments because they are unmyelinated, express a wide range of receptors, form small en passant synapses typical of the central nervous system, and have a simple and regular morphology. However, in the future these approaches can easily be applied to a wide range of presynaptic receptors and channels expressed in other axons throughout the CNS.
The axon is generally a very long, thin compartment that is electrically remote from the soma making it difficult to study axonal signaling using standard techniques. To overcome these challenges, we use modern optical techniques (two-photon calcium imaging and ligand uncaging, voltage imaging, and optogenetics) paired with standard patch-clamp electrophysiology in acute brain slices. I am currently looking for additional lab staff at all levels: lab techs, graduate students, or post-docs. Contact me if you are interested.
Pugh, J.R., and Jahr, C.E. (2013) Activation of axonal receptors by GABA spillover increases somatic firing. J Neurosci. In Press
Pugh, J.R., and Jahr, C.E. (2011) Axonal GABAA receptors increase cerebellar granule cell excitability and synaptic activity. J Neurosci. 31: 565 - 574
Pugh, J.R., and Jahr, C.E. (2011) NMDA receptor agonists fail to alter release from cerebellar basket cells. J Neurosci. 31(46): 16550-55.