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John Disterhoft
Title: Professor
Research area: The Hippocampus, Learning, and Aging
Degree: Ph.D.
Voice: 312.503.7982
Fax: 312.503.7912
e-mail: jdisterhoft@northwestern.edu

Detailed research description:
We are analyzing the neurobiology of associative learning in the mammalian brain at cellular and systems levels using both in vivo and in vitro techniques. Eyeblink conditioning is used as a model Pavlovian behavioral paradigm, as it offers excellent stimulus control, ease of precise behavioral measurement, and robust associative learning. Our program focuses on characterizing the ways in which neurons store new information during associative learning at the cellular and subcellular levels.

Experiments focus on the hippocampus, a paleocortical region involved in transferring information during learning from the short- to long-term memory store. Single neuron recording in the conscious rabbit is used to localize and functionally characterize the cell types involved in laying down the "memory trace" in the hippocampus. In parallel experiments, we make biophysical measurements from hippocampal brain slices taken from eyeblink-trained animals to define what ionic mechanisms underlie the changes in neuronal excitability recorded in the intact animal. We have observed conditioning-specific alterations in postsynaptic intrinsic currents likely to enhance cellular excitability and are performing current and whole-cell patch clamp recordings to characterize them and their relation to acquisition and consolidation of the eyeblink-conditioned response.

An important focus of our research is on cellular mechanisms for altered learning in aging. We are using a combination of behavioral and biophysical approaches to address this question. We have evaluated several pharmacological agents designed to compensate for cellular changes that we have identified in the aging brain. These behavioral pharmacological experiments are combined with neurophysiological and biophysical analyses to explore the cellular mechanisms by which the drugs may be operating to enhance learning rate in aging animals.

Other ongoing and developing experimental lines include functional magnetic resonance imaging in rabbits and humans; eyeblink conditioning combined with other cognitive evaluations in young, aging, and neurologically impaired humans; development of eyeblink conditioning and other behavioral tasks in the mouse so that we may examine aged, transgenic, and knockout strains of mice behaviorally, biophysically, and with pharmacological agents.

Representative publications:

McEchron, M.M., Boumeester, H., Tseng, W., Weiss, C.
  and Disterhoft, J.F. Hippocampectomy disrupts auditory-
  trace fear conditioning and contextual fear conditioning in
  the rat. Hippocampus, 1998, 8, 638-646.

Weiss, C., Shroff, A. and Disterhoft, J.F. Spatial learning
  and memory in aging C57BL/6 mice. Neuroscience
  Research Communications, 1998, 23, 77-92.

Disterhoft, J.F., Kronforst-Collins, M., Oh, M.M., Power,
  J.M., Preston, A.R. and Weiss, C. Cholinergic facilitation
  of trace eyeblink conditioning in aging rabbits. Life
  Sciences, 1999, 64, 541-548.

Kwon, J.Y., Bacher, A., Deyo, D.J., Grafe, M.R.,
  Disterhoft, J.F., Uchida, T. and Zornow, M.H. Effects of
  hypothermia and lamotrigine on trace conditioned learning
  after global cerebral ischemia in rabbits. Experimental
  Neurology, 1999, 159, 105-113.

LaBar, K.S. and Disterhoft, J.F. Conditioning, awareness,
  and the hippocampus. Hippocampus, 1998, 8, 620-626.

McEchron, M.M. and Disterhoft, J.F. Hippocampal
  encoding of nonspatial trace conditioning. Hippocampus,
  1999, 9, 385-396.

McGlinchey-Berroth, R., Brawn, C. and Disterhoft, J.F.
  Temporal discrimination learning in severe amnesics
  reveals an alteration in the timing of eyeblink conditioned   responses. Behavioral Neuroscience, 1999, 113, 10-18.

Oh, M.M., Power, J.M., Thompson, L.T. and
  Disterhoft, J.F. Metrifonate increases neuronal excitability
  in CA1pyramidal neurons from both young and aging rabbit
  hippocampus. Journal of Neuroscience, 1999, 19, 1814-
  1823.

Weiss, C., Bouwmeester, H., Power, J.M. and Disterhoft,
  J.F. Hippocampal lesions prevent trace eyeblink
  conditioning in the freely moving rat. Behavioral Brain
  Research, 1999, 99, 123-132.

Weiss, C., Knuttinen, M-G, Power, J.M., Patel, R.I.,
  O’Connor, M.S. and Disterhoft, J.F. Trace eyeblink
  conditioning in the freely moving rat: Optimizing the
  conditioning parameters. Behavioral Neuroscience, 1999,
  113, 1100-1105.

Geinisman, Y., Disterhoft, J.F., Gundersen, H.J.G.,
  McEchron, M.D., Persina, I.S., Power, J.M., Van der Zee,
  E.A. and West, M.J. Structural substrate of hippocampus-
  dependent associative learning: Remodeling of synapses.
  Journal of Comparative Neurology, 2000, 417, 49-59.

Kwon, J.Y., Bacher, A., Deyo, D.J., Disterhoft, J.F.,
  Zornow, M.H. The effects of pentobarbital and isoflurane on
  conditioned learning after transient global cerebral ischemia
  in rabbits. Anesthesiology, 2000, 92, 171-177.

Weiss, C., Preston, A.R., Oh, M.M., Schwarz, R.D., Welty,
  D. and Disterhoft, J.F. The M1 muscarinic agonist
  CI-1017facilitates trace eyeblink conditioning in aging
  rabbits and increases the excitability of CA1 pyramidal
  neurons. Journal of Neuroscience, 2000, 20, 783-790.

Brawn, C.M., McGlinchey-Berroth,R., Cermak, L.S. and
  Disterhoft, J.F. Cerebellar cortical degeneration disrupts
  discrimination learning but not delay or trace classical
  eyeblink conditioning. Soc. Neuroscience Abstracts,
  1998, 24, 164.

Disterhoft, J.F., McEchron, M.D., Bouwmeester, H.,
  Tseng, W., Weiss, C. and DalCanto, M.C.
  Hippocampectomy disrupts trace and contextual fear
  conditioning in the rat. Soc. Neuroscience Abstracts, 1998,
  24, 1902.

Geinisman, Y., Disterhoft, J.F., Gundersen, H.J.G.,
  McEchron, M.D., Persina, I.S., Power, J.M., Van der Zee,
  E.A. and West, M.J. Trace eyeblink conditioning induces a
  restructuring of preexisting synapses, rather than
  synaptogenesis. Soc. Neuroscience Abstracts, 1998, 24,
  1422.

Knuttinen, M-G., Weiss, C., Power, J.M., Preston, A.R. and
  Disterhoft, J.F. Senescent rats are impaired in trace and
  delay eyeblink conditioning. Soc. Neuroscience Abstracts,
  1998, 24, 443.

McEchron, M.D., Weible, A.P. and Disterhoft, J.F. Aging-
  related alterations in the covariance of CA1 hippocampal
  single neuron activity in local ensembles during trace
  eyeblink conditioning in the rabbit. Soc. Neuroscience
  Abstracts, 1998, 24, 1914.

McGlinchey-Berroth,R., Brawn, C. and Disterhoft, J.F.
  Impaired timing of conditioned responses in a temporal
  discrimination task in bitemporal amnesia. Soc.
  Neuroscience Abstracts, 1998, 24, 164.

Oh, M.M., Power, J.M., Thompson, L.T., Moriearty, P.L. and
  Disterhoft, J.F. Metrifonate increases CA1 neuronal
  excitability. Soc. Neuroscience Abstracts, 1998, 24, 1335.

Power, J.M., Oh, M.M. and Disterhoft, J.F. Metrifonate
  decreases the slow AHP current in CA1 neurons in vitro.
  Soc. Neuroscience Abstracts, 1998, 24, 1334.

Weible, A.P., McEchron, M.D., Berry, R.W. and Disterhoft,
  J.F. Retrosplenial cortex lesions impair acquisition of trace
  eyeblink conditioning. Soc. Neuroscience Abstracts, 1998,
  24, 442.

Weiss, C., Knuttinen, M-G., Power, J.M., Patel, R.I.,
  O’Connor, M.S. and Disterhoft, J.F. Eyeblink conditioning
  in the freely moving rat: A parametric study. Soc.
  Neuroscience Abstracts, 1998, 24, 443.

Zornow, M.H., Kwon, J.Y., Bacher, A. Disterhoft, J.F.,
  Grafe, M.R., Uchida, T. and Deyo, D.J. Trace conditioning
  after global cerebral ischemia in rabbits: Effects of
  hypothermia and a sodium channel antagonist. Soc.
  Neuroscience Abstracts, 1998, 24, 2146.

Wyrwicz, A.M., Chen, N-k, Li, L., Weiss, C. and Disterhoft,
  J.F. Functional MRI of visual system activation in the
  conscious rabbit. Presented at the ISMRM Conference,
  May, 1999, Philadelphia, PA.

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