Paul B. Manis, PhD
Professor

Education:

BS, California Institute of Technology, 1976
PhD, University of Florida 1981
Cellular Mechanisms of Auditory Information Processing

Cellular Mechanisms of Auditory Information Processing

Figure 1 (click for larger image & description)

Our fundamental interest is to understand the cellular mechanisms used by the nervous system to process and analyze information about the sensory environment. Sensory systems have proven to be excellent experimental systems to s tudy neural information processing, because information processing is often easily traced from one level to the next, the external stimulus can be well controlled, and the constraints of the system and requirements for specific types of processing are often readily discernable. The auditory system has provided insights into the roles of different ion channel and neurotransmitter receptor proteins in information processing, in part because of the specialized requirements for exquisite control of action potential timing in response to acoustic stimuli.

One long-term focus in the lab is the dynamic electrical signaling of individual neurons as regulated by ion channels and their distribution on the cell membrane. For example, we have identified low-threshold activating potassium channels that dominate the membrane properties of some cochlear nucleus neurons, and play a critical role in relaying the precise temporal information needed for azimuthal sound localization and speech discrimination to higher auditory centers. We have carefully characterized these channels and have developed kinetic models that help to explain the role of the channels in auditory information processing. We are currently trying to identify the potassium channel subunits that form this conductance. In another area of the cochlear nucleus, neurons integrate information from a variety of sources, both auditory and non- auditory, and have complex acoustic response properties. We have been studying the intrinsic ion channels that regulate the discharge patterns of these cells, and now suggest that these cells exhibit state-dependent discharge patterns that depend on both a transient potassium channel and a non-inactivation sodium conductance. Current studies are examining the contributions of these channels under different membrane states and in response to synthesized synaptic inputs. We are also working to identify the specific genes responsible for the transient potassium current.

A second area of interest is the communication between neurons that takes place largely at synapses, including the mechanisms and timing requirements of normal synaptic plasticity as well as changes in synaptic function that occurs during deafness. In recent experiments, we have found changes in receptor composition and function in the cochlear nucleus resulting from deafness in a strain of mice with an early onset high frequency hearing loss. A new direction that we are taking is to examine neural circuit organization and synaptic plasticity in cortex. In these experiments, we are studying spike-timing dependent synaptic plasticity at specific sets of synapses in auditory cortex, to test hypotheses regarding the plasticity in cortical organization can result from altered acoustic environments during development and critical periods.

Publications:

Kanold PO, Manis PB.(2004) Encoding the timing of inhibitory inputs. J Neurophysiol. 2004 Dec 29

Manis PB, Molitor SC, Wu H. (2003) Subthreshold oscillations generated by TTX-sensitive sodium currents in dorsal cochlear nucleus pyramidal cells. Exp Brain Res. 153(4):443-51.

Molitor SC, Manis PB (2003) Dendritic Ca2+ transients evoked by action potentials in rat dorsal cochlear nucleus pyramidal and cartwheel neurons. J Neurophysiol 89: 2225-2237.

Rothman JS, Manis PB (2003) Differential expression of three distinct potassium currents in the ventral cochlear nucleus. J Neurophysiol 89: 3070-3082

Rothman JS, Manis PB (2003) Kinetic analyses of three distinct potassium conductances in ventral cochlear nucleus neurons. J Neurophysiol 89: 3083-3096

Rothman JS, Manis PB (2003) The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons. J Neurophysiol 89: 3097-3113

Francis HW, Scott JC, Manis PB (2002) Protein kinase C mediates potentiation of synaptic transmission by phorbol ester at parallel fibers in the dorsal cochlear nucleus. Brain Res 951: 9-22

Kanold PO, Manis PB (2001) A physiologically based model of discharge pattern regulation by transient K+ currents in cochlear nucleus pyramidal cells. J Neurophysiol 85: 523-538

Aizenman CD, Huang EJ, Manis PB, Linden DJ (2000) Use-dependent changes in synaptic strength at the Purkinje cell to deep nuclear synapse. Prog Brain Res 124: 257-273

Francis HW, Manis PB (2000) Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons. Hear Res 149: 91-105

Cunningham AM, Manis PB, Reed RR, Ronnett GV (1999) Olfactory receptor neurons exist as distinct subclasses of immature and mature cells in primary culture. Neuroscience 93: 1301-1312

Kanold PO, Manis PB (1999) Transient potassium currents regulate the discharge patterns of dorsal cochlear nucleus pyramidal cells. J Neurosci 19: 2195-2208

Molitor SC, Manis PB (1999) Voltage-gated Ca2+ conductances in acutely isolated guinea pig dorsal cochlear nucleus neurons. J Neurophysiol 81: 985-998

Aizenman CD, Manis PB, Linden DJ (1998) Polarity of long-term synaptic gain change is related to postsynaptic spike firing at a cerebellar inhibitory synapse. Neuron 21: 827-835

Harty TP, Manis PB (1998) Kinetic analysis of glycine receptor currents in ventral cochlear nucleus. J Neurophysiol 79: 1891-1901