Donald A Wilson

Publications (128) View all

• Article: Cholinergic modulation of olfactory pattern separation.

  Julie Chapuis, Donald A Wilson
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  ABSTRACT: Pattern separation plays an important role in perception and memory. In olfaction, pattern separation is critical component of piriform cortical odor processing contributing to behavioral perception of overlapping odor mixtures. Previous work has demonstrated that odor discrimination ability is modulated by acetylcholine. Here, we extended this previous work by using a distinct, well characterized complex odor stimulus set that has been shown to differentially involve pattern separation processes within piriform cortex. We find that the cholinergic muscarinic receptor agonist oxotremorine facilitates the acquisition of odor discrimination. Furthermore, the muscarinic receptor antagonist scopolamine impairs acquisition of odor discrimination even if the antagonist is limited to the piriform cortex. Finally, acetylcholine effects are most robust during discrimination acquisition, with minimal effects during expression.
  Neuroscience Letters 04/2013; · 2.11 Impact Factor
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  Available from: Donald A Wilson

  Article: Running just to stand still.

  Donald A Wilson
  Nature Neuroscience 08/2012; 15(9):1175-6. · 15.53 Impact Factor
• Article: Odor-evoked activity in the mouse lateral entorhinal cortex.

  W Xu, D A Wilson
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  ABSTRACT: The entorhinal cortex is a brain area with multiple reciprocal connections to the hippocampus, amygdala, perirhinal cortex, olfactory bulb and piriform cortex. As such, it is thought to play a large role in the olfactory memory process. The present study is the first to compare lateral entorhinal and anterior piriform cortex odor-evoked single-unit and local field potential activity in mouse. Recordings were made in urethane-anesthetized mice that were administered a range of three pure odors and three overlapping odor mixtures. Results show that spontaneous as well as odor-evoked unit activity was lower in lateral entorhinal versus piriform cortex. In addition, units in lateral entorhinal cortex were responsive to a more restricted set of odors compared to piriform. Conversely, odor-evoked power change in local field potential activity was greater in the lateral entorhinal cortex in the theta band than in piriform. The highly odor-specific and restricted firing in lateral entorhinal cortex suggests that it may play a role in modulating odor-specific, experience- and state-dependent olfactory coding.
  Neuroscience 08/2012; 223:12-20. · 3.38 Impact Factor
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  Available from: Donald A Wilson

  Article: Immunization targeting a minor plaque constituent clears β-amyloid and rescues behavioral deficits in an Alzheimer's disease mouse model.

  Jose Morales-Corraliza, Stephen D Schmidt, Matthew J Mazzella, Jason D Berger, Donald A Wilson, Daniel W Wesson, Mathias Jucker, Efrat Levy, Ralph A Nixon, Paul M Mathews
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  ABSTRACT: Although anti-human β-amyloid (Aβ) immunotherapy clears brain β-amyloid plaques in Alzheimer's disease (AD), targeting additional brain plaque constituents to promote clearance has not been attempted. Endogenous murine Aβ is a minor Aβ plaque component in amyloid precursor protein (APP) transgenic AD models, which we show is ∼3%-8% of the total accumulated Aβ in various human APP transgenic mice. Murine Aβ codeposits and colocalizes with human Aβ in amyloid plaques, and the two Aβ species coimmunoprecipitate together from brain extracts. In the human APP transgenic mouse model Tg2576, passive immunization for 8 weeks with a murine-Aβ-specific antibody reduced β-amyloid plaque pathology, robustly decreasing both murine and human Aβ levels. The immunized mice additionally showed improvements in two behavioral assays, odor habituation and nesting behavior. We conclude that passive anti-murine Aβ immunization clears Aβ plaque pathology-including the major human Aβ component-and decreases behavioral deficits, arguing that targeting minor endogenous brain plaque constituents can be beneficial, broadening the range of plaque-associated targets for AD therapeutics.
  Neurobiology of aging 05/2012; · 5.94 Impact Factor
• Article: ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.

  Paige E Cramer, John R Cirrito, Daniel W Wesson, C Y Daniel Lee, J Colleen Karlo, Adriana E Zinn, Brad T Casali, Jessica L Restivo, Whitney D Goebel, Michael J James, Kurt R Brunden, Donald A Wilson, Gary E Landreth
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  ABSTRACT: Alzheimer's disease (AD) is associated with impaired clearance of β-amyloid (Aβ) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the rapid reversal of a broad range of Aβ-induced deficits.
  Science 02/2012; 335(6075):1503-6. · 31.20 Impact Factor