Daniel W Wesson

Case Western Reserve University School of Medicine , Cleveland, OH, United States

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Publications (35)255.39 Total impact

  • Daniel W Wesson
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    ABSTRACT: Sniffing has historically been considered an olfactory behavior because inhalation is a necessary step in odor perception. Growing evidence, however, has demonstrated that the display of sniffing surpasses the bounds of those contexts that are olfactory in nature. In this issue of Chemical Senses, Arzi, Shedlesky, Secundo, and Sobel demonstrate that humans mimic visually and auditory-observed sniffing, independent of experimentally applied olfactory sensory input. These findings raise important and exciting questions about the possible roles of sniffing in the social context and highlight the need for chemosensory researchers to reconsider the significance of sniffing.
    Chemical Senses 03/2014; · 3.22 Impact Factor
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    ABSTRACT: The olfactory tubercle (OT), a trilaminar structure located in the basal forebrain of mammals, is thought to play an important role in olfaction. While evidence has accumulated regarding the contributions of the OT to odor information processing, studies exploring the role of the OT in olfaction in awake animals remain unavailable. In the present study, we begin to address this void through multi-day recordings of local field potential (LFP) activity within the OT of awake, freely exploring Long-Evans rats. We observed spontaneous OT LFP activity consisting of theta- (2-12Hz), beta- (15-35Hz) and gamma- (40-80Hz) band activity - characteristic of previous reports of LFPs in other principle olfactory structures. Beta- and gamma-band powers were enhanced upon odor presentation. Simultaneous recordings of OT and upstream olfactory bulb (OB) LFPs revealed odor-evoked LFP power at statistically similar levels in both structures. Strong spectral coherence was observed between the OT and OB during both spontaneous and odor-evoked states. Further, the OB theta rhythm more strongly cohered with the respiratory rhythm and respiratory-coupled theta cycles in the OT occurred following theta cycles in the OB. Finally, we found that the animal's internal state modulated LFP activity in the OT. Together, these data provide initial insights into the network activity of the OT in the awake rat, including spontaneous rhythmicity, odor-evoked modulation, connectivity with upstream sensory input, and state-dependent modulation.
    Journal of Neurophysiology 03/2014; · 3.30 Impact Factor
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    ABSTRACT: Rodents show robust behavioral responses to odors, including strong preferences or aversions for certain odors. The neural mechanisms underlying the effects of odors on these behaviors in animals are not well understood. Here, we provide an initial proof-of-concept study into the role of the olfactory tubercle (OT), a structure with known anatomical connectivity with both brain reward and olfactory structures, in regulating odor-motivated behaviors. We implanted c57bl/6 male mice with an ipsilateral bipolar electrode into the OT to administer electric current and thereby yield gross activation of the OT. We confirmed that electrical stimulation of the OT was rewarding, with mice frequently self-administering stimulation on a fixed ratio schedule. In a separate experiment, mice were presented with either fox urine or peanut odors in a three-chamber preference test. In absence of OT stimulation, significant preference for the peanut odor chamber was observed which was abolished in the presence of OT stimulation. Perhaps providing a foundation for this modulation in behavior, we found that OT stimulation significantly increased the number of c-Fos positive neurons in not only the OT, but also in forebrain structures essential to motivated behaviors, including the nucleus accumbens and lateral septum. The present results support the notion that the OT is integral to the display of motivated behavior and possesses the capacity to modulate odor hedonics either by directly altering odor processing or perhaps by indirect actions on brain reward and motivation structures.
    Frontiers in Behavioral Neuroscience 01/2014; 8:81. · 4.76 Impact Factor
  • Daniel W Wesson
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    ABSTRACT: Animals have evolved behavioral and neural specializations which are optimal for survival within their respective physical environments. I recently proposed [1] that socially interacting rats may monitor each other's sniffing through perception of subtle auditory and/or tactile cues given off by the act of sniffing and further hypothesized the "likely possibility that reciprocal sniffing behavior coincides with other established forms of communication (ultrasonic vocalizations, odor emission) that together allow optimal intraspecific communication". Assini et al.[2] provide a timely test of this hypothesis, and in doing so, show that reciprocal sniffing behavior [1] and ultrasonic vocalizations coincide in their display by submissive rats. Here I attempt to frame these two supportive studies together with the goal of a greater understanding of animal social cognition and communication.
    Current biology: CB 11/2013; 23(22):R997-R998. · 10.99 Impact Factor
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    ABSTRACT: Intranasal trigeminal sensory input, often perceived as a burning, tingling, or stinging sensation, is well known to affect odor perception. While both anatomical and functional imaging data suggest that the influence of trigeminal stimuli on odor information processing may occur within the olfactory cortex, direct electrophysiological evidence for the encoding of trigeminal information at this level of processing is unavailable. Here, in agreement with human functional imaging studies, we found that 26% of neurons in the mouse piriform cortex (PCX) display modulation in firing to carbon dioxide (CO2), an odorless stimulant with known trigeminal capacity. Interestingly, CO2 was represented within the PCX by distinct temporal dynamics, differing from those evoked by odor. Experiments with ascending concentrations of isopentyl acetate, an odorant known to elicit both olfactory and trigeminal sensations, resulted in morphing of the temporal dynamics of stimulus-evoked responses. Whereas low concentrations of odorant evoked responses upon stimulus onset, high concentrations of odorant and/or CO2 often evoked responses structured to stimulus offset. These physiological experiments in mice suggest that PCX neurons possess the capacity to encode for stimulus modality (olfactory vs trigeminal) by differential patterns of firing. These data provide mechanistic insights into the influences of trigeminal information on odor processing and place constraints on models of olfactory-trigeminal sensory integration.
    Journal of Neuroscience 08/2013; 33(34):13873-81. · 6.91 Impact Factor
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    ABSTRACT: The incidence of olfactory perceptual dysfunction increases substantially with aging. Putative mechanisms for olfactory sensory loss are surfacing, including neuroanatomical modifications within brain regions responsible for odor information processing. The islands of Calleja (IC) are dense cell clusters localized within the olfactory tubercle, a cortical structure receiving monosynaptic input from the olfactory bulb. The IC are hypothesized to be important for intra- and extra-olfactory tubercle information processing, and thus olfaction. However, whether the anatomy of the IC are affected throughout normal aging remains unclear. By examining the IC of C57bl/6 mice throughout adulthood and early aging (4-18 months of age), we found that the number of IC decreases significantly with aging. Stereological analysis revealed that the remaining IC in 18-month-old mice were significantly reduced in estimated volume compared with those in 4- month-old mice. We additionally found that whereas young adults (4 months of age) possess greater numbers of IC within the posterior parts of the olfactory tubercle, by 18 months of age, a greater percentage of IC are found within the anterior-most part of the olfactory tubercle, perhaps providing a substrate for the differential access of the IC to odor information throughout aging. These results show that the IC are highly plastic components of the olfactory cortex, changing in volume, localization, and even number throughout normal aging. We predict that modifications among the IC throughout aging and age-related neurodegenerative disorders might be a novel contributor to pathological changes in olfactory cortex function and olfactory perception.
    Neurobiology of aging 06/2013; · 5.94 Impact Factor
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    ABSTRACT: The data reported in the Technical Comments by Fitz et al., Price et al., Tesseur et al., and Veeraraghavalu et al. replicate and validate our central conclusion that bexarotene stimulates the clearance of soluble β-amyloid peptides and results in the reversal of behavioral deficits in mouse models of Alzheimer's disease (AD). The basis of the inability to reproduce the drug-stimulated microglial-mediated reduction in plaque burden is unexplained. However, we concluded that plaque burden is functionally unrelated to improved cognition and memory elicited by bexarotene.
    Science 05/2013; 340(6135):924. · 31.20 Impact Factor
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    ABSTRACT: Understanding central processing requires precise monitoring of neural activity across populations of identified neurons in the intact brain. In the present study, we used recently optimized variants of the genetically encoded calcium sensor GCaMP (GCaMP3 and GCaMPG5G) to image activity among genetically and anatomically defined neuronal populations in the olfactory bulb (OB), including two types of GABAergic interneurons (periglomerular [PG] and short axon [SA] cells) and OB output neurons (mitral/tufted [MT] cells) projecting to the piriform cortex. We first established that changes in neuronal spiking can be related accurately to GCaMP fluorescence changes via a simple quantitative relationship over a large dynamic range. We next used in vivo two-photon imaging from individual neurons and epifluorescence signals reflecting population-level activity to investigate the spatiotemporal representation of odorants across these neuron types in anesthetized and awake mice. Under anesthesia, individual PG and SA cells showed temporally simple responses and little spontaneous activity, whereas MT cells were spontaneously active and showed diverse temporal responses. At the population level, response patterns of PG, SA, and MT cells were surprisingly similar to those imaged from sensory inputs, with shared odorant-specific topography across the dorsal OB and inhalation-coupled temporal dynamics. During wakefulness, PG and SA cell responses increased in magnitude but remained temporally simple, whereas those of MT cells changed to complex spatiotemporal patterns reflecting restricted excitation and widespread inhibition. These results suggest multiple circuit elements with distinct roles in transforming odor representations in the OB and provide a framework for further study of early olfactory processing using optical and genetic tools.
    Journal of Neuroscience 03/2013; 33(12):5285-300. · 6.91 Impact Factor
  • Daniel W Wesson
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    ABSTRACT: Sniffing is a specialized respiratory behavior that is essential for the acquisition of odors [1-4]. Perhaps not independent of this, sniffing is commonly displayed during motivated [5-7] and social behaviors [8, 9]. No measures of sniffing among interacting animals are available, however, calling into question the utility of this behavior in the social context. From radiotelemetry recordings of nasal respiration, I found that investigation by one rat toward the facial region of a conspecific often elicits a decrease in sniffing frequency in the conspecific. This reciprocal display of sniffing was found to be dependent upon the rat's social status in two separate paradigms, with subordinates reliably decreasing their sniffing frequency upon being investigated in the face by dominant rats. Failure of subordinates to decrease their sniffing frequency shortened the latency for agonistic behavior by dominant rats, reflecting that decreases in sniffing serve as appeasement signals during social interactions. Rats rendered unable to smell persisted in displaying reciprocal sniffing behavior, demonstrating the independence of this behavior from olfaction. Oxytocin treatment in rats with established social hierarchies abolished agonistic behaviors and reciprocal sniffing displays. Together, these findings demonstrate that rodents utilize sniffing behaviors communicatively, not only to collect [6, 10-14] but also to convey information.
    Current biology: CB 03/2013; · 10.99 Impact Factor
  • Adrienn G Varga, Daniel W Wesson
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    ABSTRACT: The mammalian olfactory cortex is commonly considered critical for odor information processing and perception. It is becoming increasingly apparent, however, that the olfactory cortex receives input from multiple sensory channels. Previous work from our group demonstrated the presence of auditory sensory convergence within one olfactory cortical structure, the olfactory tubercle (OT). Interestingly, anatomical evidence for auditory input into the neighboring olfactory piriform cortex (PCX) posits the possibility that auditory sensory input is a distributed property of the olfactory cortex. To address this question, we performed in vivo extracellular recordings from the OT and PCX of anesthetized mice and measured modulations in unit firing in the presence of tones. In support for auditory sensory input being a distributed feature of the olfactory cortex, we found that 29% of units sampled within the PCX display tone-evoked responses. This population compares with that found within the OT using the same stimuli (37%). While overall tone-evoked response magnitudes were comparable between the two structures, tone signal : noise was significantly greater within the OT than in the PCX. No effect of tone frequency (1-55 kHz) was found within either structure, with most units being narrowly tuned to a single frequency. These results suggest that a major portion of odor-evoked output from the olfactory bulb (i.e. that entering the OT and PCX) is subject to auditory sensory input in a manner that may modulate odor information processing, odor-guided behaviors and perception.
    European Journal of Neuroscience 11/2012; · 3.75 Impact Factor
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    ABSTRACT: Olfaction is often impaired in Alzheimer's disease (AD) and is also dysfunctional in mouse models of the disease. We recently demonstrated that short-term passive anti-murine-Aβ immunization can rescue olfactory behavior in the Tg2576 mouse model overexpressing a human mutation of the amyloid precursor protein (APP) after β-amyloid deposition. Here we tested the ability to preserve normal olfactory behaviors by means of long-term passive anti-murine-Aβ immunization. Seven-month-old Tg2576 and non-transgenic littermate (NTg) mice were IP-injected biweekly with the m3.2 murine-Aβ-specific antibody until 16 mo of age when mice were tested in the odor habituation test. While Tg2576 mice treated with a control antibody showed elevations in odor investigation times and impaired odor habituation compared to NTg, olfactory behavior was preserved to NTg levels in m3.2-immunized Tg2576 mice. Immunized Tg2576 mice had significantly less β-amyloid immunolabeling in the olfactory bulb and entorhinal cortex, yet showed elevations in Thioflavin-S labeled plaques in the piriform cortex. No detectable changes in APP metabolite levels other than Aβ were found following m3.2 immunization. These results demonstrate efficacy of chronic, long-term anti-murine-Aβ m3.2 immunization in preserving normal odor-guided behaviors in a human APP Tg model. Further, these results provide mechanistic insights into olfactory dysfunction as a biomarker for AD by yielding evidence that focal reductions of Aβ may be sufficient to preserve olfaction.
    Behavioural brain research 09/2012; 237:96–102. · 3.22 Impact Factor
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    Colleen A Payton, Donald A Wilson, Daniel W Wesson
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    ABSTRACT: The olfactory cortex encompasses several anatomically distinct regions each hypothesized to provide differential representation and processing of specific odors. Studies exploring whether or not the diversity of olfactory bulb input to olfactory cortices has functional meaning, however, are lacking. Here we tested whether two anatomically major olfactory cortical structures, the olfactory tubercle (OT) and piriform cortex (PCX), differ in their neural representation and processing dynamics of a small set of diverse odors by performing in vivo extracellular recordings from the OT and PCX of anesthetized mice. We found a wealth of similarities between structures, including odor-evoked response magnitudes, breadth of odor tuning, and odor-evoked firing latencies. In contrast, only few differences between structures were found, including spontaneous activity rates and odor signal-to-noise ratios. These results suggest that despite major anatomical differences in innervation by olfactory bulb mitral/tufted cells, the basic features of odor representation and processing, at least within this limited odor set, are similar within the OT and PCX. We predict that the olfactory code follows a distributed processing stream in transmitting behaviorally and perceptually-relevant information from low-level stations.
    PLoS ONE 08/2012; 7(4):e34926. · 3.53 Impact Factor
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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
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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
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    ABSTRACT: The unique vulnerability of the olfactory system to Alzheimer's disease (AD) provides a quintessential translational tool for understanding mechanisms of synaptic dysfunction and pathological progression in the disease. Using the Tg2576 mouse model of β-amyloidosis, we show that aberrant, hyperactive olfactory network activity begins early in life, before detectable behavioral impairments or comparable hippocampal dysfunction and at a time when amyloid-β (Aβ) deposition is restricted to the olfactory bulb (OB). Hyperactive odor-evoked activity in the piriform cortex (PCX) and increased OB-PCX functional connectivity emerged at a time coinciding with olfactory behavior impairments. This hyperactive activity persisted until later in life when the network converted to a hyporesponsive state. This conversion was Aβ-dependent, because liver-X receptor agonist treatment to promote Aβ degradation rescued the hyporesponsive state and olfactory behavior. These data lend evidence to a novel working model of olfactory dysfunction in AD and, complimentary to other recent works, suggest that disease-relevant network dysfunction is highly dynamic and region specific, yet with lasting effects on cognition and behavior.
    Journal of Neuroscience 11/2011; 31(44):15962-71. · 6.91 Impact Factor
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    ABSTRACT: Orienting responses are physiological and active behavioral reactions evoked by novel stimulus perception and are critical for survival. We explored whether odor orienting responses are impacted throughout both adulthood and normal and pathological aging in mice. Novel odor investigation (including duration and bout numbers) and its subsequent habituation as assayed in the odor habituation task were preserved in adult C57BL/6J mice up to 12 mo of age with <6% variability between age groups in investigation time. Separately, using whole-body plethysmography we found that both spontaneous respiration and odor-evoked sniffing behaviors were strikingly preserved in wildtype (WT) mice up to 26 mo of age. In contrast, mice accumulating amyloid-β protein in the brain by means of overexpressing mutations in the human amyloid precursor protein gene (APP) showed preserved spontaneous respiration up to 12 mo, but starting at 14 mo showed significant differences from WT. Similar to WTs, odor-evoked sniffing was not impacted in APP mice up to 26 mo. These results show that odor-orienting responses are minimally impacted throughout aging in mice, and suggest that the olfactomotor network is mostly spared of insults due to aging.
    Behavioural brain research 09/2011; 223(1):99-106. · 3.22 Impact Factor
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    ABSTRACT: The extensive autophagic-lysosomal pathology in Alzheimer disease (AD) brain has revealed a major defect: in the proteolytic clearance of autophagy substrates. Autophagy failure contributes on several levels to AD pathogenesis and has become an important therapeutic target for AD and other neurodegenerative diseases. We recently observed broad therapeutic effects of stimulating autophagic-lysosomal proteolysis in the TgCRND8 mouse model of AD that exhibits defective proteolytic clearance of autophagic substrates, robust intralysosomal amyloid-β peptide (Aβ) accumulation, extracellular β-amyloid deposition and cognitive deficits. By genetically deleting the lysosomal cysteine protease inhibitor, cystatin B (CstB), to selectively restore depressed cathepsin activities, we substantially cleared Aβ, ubiquitinated proteins and other autophagic substrates from autolysosomes/lysosomes and rescued autophagic-lysosomal pathology, as well as reduced total Aβ40/42 levels and extracellular amyloid deposition, highlighting the underappreciated importance of the lysosomal system for Aβ clearance. Most importantly, lysosomal remediation prevented the marked learning and memory deficits in TgCRND8 mice. Our findings underscore the pathogenic significance of autophagic-lysosomal dysfunction in AD and demonstrate the value of reversing this dysfunction as an innovative therapeautic strategy for AD.
    Autophagy 07/2011; 7(7):788-9. · 12.04 Impact Factor
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    ABSTRACT: This review critically examines progress in understanding the link between Alzheimer's disease (AD) molecular pathogenesis and behavior, with an emphasis on the impact of amyloid-β. We present the argument that the AD research field requires more multifaceted analyses into the impacts of Alzheimer's pathogenesis which combine simultaneous molecular-, circuit-, and behavior-level approaches. Supporting this argument is a review of particular research utilizing similar, "systems-level" methods in mouse models of AD. Related to this, a critique of common physiological and behavioral models is made-highlighting the likely usefulness of more refined and specific tools in understanding the relationship between candidate molecular pathologies and behavioral dysfunction. Finally, we propose challenges for future research which, if met, may greatly extend our current understanding of how AD molecular pathology impacts neural network function and behavior and possibly may lead to refinements in disease therapeutics.
    Molecular Neurobiology 03/2011; 43(3):163-79. · 5.47 Impact Factor
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    Colleen A Payton, Daniel W Wesson
    Frontiers in Neuroanatomy 01/2011; 5:61. · 4.06 Impact Factor
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    Daniel W Wesson, Donald A Wilson
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    ABSTRACT: Since its designation in 1896 as a putative olfactory structure, the olfactory tubercle has received little attention in terms of elucidating its role in the processing and perception of odors. Instead, research on the olfactory tubercle has mostly focused on its relationship with the reward system. Here we provide a comprehensive review of research on the olfactory tubercle-with an emphasis on the likely role of this region in olfactory processing and its contributions to perception. Further, we propose several testable hypotheses regarding the likely involvement of the olfactory tubercle in both basic (odor detection, discrimination, parallel processing of olfactory information) and higher-order (social odor processing, hedonics, multi-modal integration) functions. Together, the information within this review highlights an understudied yet potentially critical component in central odor processing.
    Neuroscience & Biobehavioral Reviews 01/2011; 35(3):655-68. · 10.28 Impact Factor

Publication Stats

949 Citations
255.39 Total Impact Points

Institutions

  • 2012–2013
    • Case Western Reserve University School of Medicine
      • Department of Neurosciences
      Cleveland, OH, United States
  • 2011–2013
    • Case Western Reserve University
      • Department of Neurosciences
      Cleveland, OH, United States
  • 2010–2011
    • Nathan Kline Institute
      Orangeburg, New York, United States
  • 2006–2009
    • Boston University
      • Department of Biology
      Boston, MA, United States
    • University of Texas at San Antonio
      • Department of Biology
      San Antonio, TX, United States