Gonzalo H. Otazu’s research while affiliated with SUNY Old Westbury and other places

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Publications (34)


(A) Head‐fixed mice were trained in a go, no‐go task to detect target odors. (B) Mice were trained with a set of known background odors. (C) Mice were tested with novel background odors. (D) Trials with novel background odors were interleaved with trials with known background odors as catch trials. (D–F) Shank3B−/+ and Cntnap2−/− mice performance for known odors matched that of the WT mice performance. (E–G) Mouse models of autism had deficits for odor recognition in novel background odors. Data are from Li et al. [59] and Ryndych et al. [60].
Role of Odor Novelty on Olfactory Issues in Autism Spectrum Disorder
  • Literature Review
  • Full-text available

December 2024

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12 Reads

Zoe A. Scheier

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Kassandra L. Sturm

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John A. Colavecchio

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Gonzalo H. Otazu

Sensory processing abnormalities are a hallmark of autism spectrum disorder (ASD) and are included in its diagnostic criteria. Among these challenges, food neophobia has garnered attention due to its prevalence and potential impact on nutritional intake and health outcomes. This review describes the correlation between novel odor perception and feeding difficulties within the context of ASD. Moreover, this review underscores the role of odor processing in shaping feeding behaviors within the ASD population. It examines the psychophysics of odor perception in individuals with ASD and evaluates the behavioral and neurophysiological assessments conducted using novel odor stimuli in mouse models relevant to autism and wild‐type mice. Additionally, we explore the mechanism on how odor novelty affects neuronal circuitry, shedding light on potential underlying mechanisms for the effect of odor novelty on ASD.

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Active Learning Exercises in Synaptic Physiology and Connectivity for the Neuroscience Lecture Hall, Laboratory Course, or Outreach Setting

December 2024

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5 Reads

Journal of Undergraduate Neuroscience Education

It is well-understood that active learning approaches have positive learning outcomes and improve retention. Active learning strategies for the neuroscience laboratory setting have been extensively developed. Fewer active learning approaches are available for the traditional lecture-based setting. Here we describe novel active learning exercises that teach fundamental principles of neuronal circuits and synaptic connectivity ideal for introductory neuroscience courses. Given the complexity of synaptic networks in the brain and the difficulty this material can present to students, our novel exercises can be beneficial to the neuroscience education community.



Seizures in Mouse Models of Autism

February 2024

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24 Reads

There is an association between Autism Spectrum Disorder (ASD) and epilepsy, as both conditions tend to appear together. In this chapter we will review factors that affect that association, as well as potential causal relationships between these two conditions as well as proposed common etiology for both conditions. We propose that studying epileptic activity in monogenic mouse models of autism will help define the origins of the association between ASD and epilepsy.


Distribution of male and female mice with normal brains or heterotopia in the neocortex and/or cerebellum.
Neocortical heterotopia in C57BL/6J mice. (A) Three examples (i–iii) of neocortical heterotopia (arrows) from mice in the current study. Heterotopia could be in the dorsal neocortex (i and iii) or at the cortical midline (ii) and was characterized by an accumulation of neurons and glia in layer 1 which would otherwise have few scattered neurons therein. High magnification of heterotopia shown in left-side panels with asterisks indicate areas of intact layer I adjacent to heterotopia. (B) Three examples (i–iii) of neocortical heterotopia taken from the Allen Mouse Brain Atlas that are nearly identical in spatial/areal location at the dorsal neocortex (i and iii) or the cortical midline (ii) scalebar for (A) (left/right) = 1,047/400 μm; (B) (left/right) = 1,500/600 μm.
Cerebellar heterotopia in C57BL/6J mice. (A) Example of an intact cerebellum (i) and two examples of cerebellar heterotopia (ii and iii) in female mice from the current study. Arrows point to normal cytoarchitecture of lobules VIII and IX (i) or heterotopic neurons and glia in between lobules VIII and IX (ii and iii). (B) Example of intact cerebellum (i) and two examples of cerebellar heterotopia (ii and iii) from male mice from the current study. (C) Example of intact cerebellum (i) and two examples of cerebellar heterotopia (ii and iii) from male mice from the Allen Mouse Brain Atlas which are nearly identical to that from the current study. Higher magnification of examples in (iii) are shown in (iv). Scalebars for (A, B) = 1,000 and 333 μm (i–iii and iv, respectively). Scalebars for (C) = 1,047 and 350 μm (i–iii and iv, respectively).
Seizure latency times for male and female mice with normal brains and heterotopia. (A) Latency to seizure (mean sec; error bars are SEM) for male C57BL/6J mice exhibiting a normal brain with no malformation, a brain with both types of malformation (Both), neocortical heterotopia only (Neocrtx only), or cerebellar heterotopia only. The numbers inside the bars reflect the number of mice in each group. (B) Latency to seizure (mean sec; error bars are SEM) for female C57BL/6J mice. Black bar and asterisk point to significant differences between selected groups. The numbers inside the bars reflect the number of mice in each group.
Neocortical and cerebellar malformations affect flurothyl-induced seizures in female C57BL/6J mice

November 2023

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59 Reads

Brain malformations cause cognitive disability and seizures in both human and animal models. Highly laminated structures such as the neocortex and cerebellum are vulnerable to malformation, affecting lamination and neuronal connectivity as well as causing heterotopia. The objective of the present study was to determine if sporadic neocortical and/or cerebellar malformations in C57BL/6J mice are correlated with reduced seizure threshold. The inhaled chemi-convulsant flurothyl was used to induce generalized, tonic-clonic seizures in male and female C57BL/6J mice, and the time to seizure onset was recorded as a functional correlate of brain excitability changes. Following seizures, mice were euthanized, and brains were extracted for histology. Cryosections of the neocortex and cerebellar vermis were stained and examined for the presence of molecular layer heterotopia as previously described in C57BL/6J mice. Over 60% of mice had neocortical and/or cerebellar heterotopia. No sex differences were observed in the prevalence of malformations. Significantly reduced seizure onset time was observed dependent on sex and the type of malformation present. These results raise important questions regarding the presence of malformations in C57BL/6J mice used in the study of brain development, epilepsy, and many other diseases of the nervous system.


Figure 4. Average odor responses were correlated between WT and Shank3B 1/À mice. A, Average glomerular responses for WT mice and Shank3B 1/À mice for a panel of 20 odors used during the behavior, with each odor presented at the concentration used during the testing phase (target odors, 0.025% of vapor pressure; background odors, 0.1% of vapor pressure). Symbols correspond to average responses from individual animals. Error bars are s.e.m. B, Average evoked responses were correlated between WT mice and Shank3B 1/À mice. C, Fraction of glomeruli whose activity exceeded the threshold per odor. D, The fraction activated per odor was correlated across genotypes.
Haploinsufficiency of Shank3 in Mice Selectively Impairs Target Odor Recognition in Novel Background Odors

September 2023

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22 Reads

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6 Citations

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

Individuals with mutations in a single copy of the SHANK3 gene present with social-interaction deficits. Although social behavior in mice depends on olfaction, mice with mutations in a single copy of the Shank3 gene do not have olfactory deficits in simple odor identification tasks (Drapeau et al. 2018). Here we tested olfaction in mice with mutations in a single copy of the Shank3 gene (Peça et al. 2011) using a complex odor-task and imaging in awake mice. Average glomerular responses in the olfactory bulb of Shank3B +/− were correlated with WT mice. However, there was increased trial-to-trial variability in the odor responses for Shank3B +/− mice. Simulations demonstrated that this increased variability could affect odor detection in novel environments. In order to test whether performance was affected by the increased variability, we tested target odor recognition in the presence of novel background odors using a recently developed task (Y. Li et al. 2023). Head-fixed mice were trained to detect target odors in the presence of known background odors. Performance was tested using catch trials where the known background odors were replaced by novel background odors. We compared the performance of 8 Shank3B +/− mice (5 males, 3 females) on this task with 6 WT mice (3 males, 3 females). Performance for known background odors and learning rates were similar between Shank3B +/− and WT mice. However, when tested with novel background odors, Shank3B +/− mice performance dropped to almost chance levels. Thus, haploinsufficiency of the Shank3 gene causes a specific deficit in odor detection in novel environments. Our results are discussed in the context of other Shank3 mouse models and have implications for understanding olfactory function in neurodevelopmental disorders. Significance Statement People and mice with mutations in a single copy in the synaptic gene Shank3 show features seen in autism spectrum disorders, including social interaction deficits. Although mice social behavior uses olfaction, mice with mutations in a single copy of Shank3 have so far not shown olfactory deficits when tested using simple tasks. Here we used a recently developed task to show that these mice could identify odors in the presence of known background odors as well as wild-type mice. However, their performance fell below wild-type mice when challenged with novel background odors. This deficit was also previously reported in the Cntnap2 mouse model of autism suggesting that odor detection in novel backgrounds is a general deficit across mouse models of autism.


Robust odor identification in novel olfactory environments in mice

February 2023

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77 Reads

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12 Citations

Relevant odors signaling food, mates, or predators can be masked by unpredictable mixtures of less relevant background odors. Here, we developed a mouse behavioral paradigm to test the role played by the novelty of the background odors. During the task, mice identified target odors in previously learned background odors and were challenged by catch trials with novel background odors, a task similar to visual CAPTCHA. Female wild-type (WT) mice could accurately identify known targets in novel background odors. WT mice performance was higher than linear classifiers and the nearest neighbor classifier trained using olfactory bulb glomerular activation patterns. Performance was more consistent with an odor deconvolution method. We also used our task to investigate the performance of female Cntnap2-/- mice, which show some autism-like behaviors. Cntnap2-/- mice had glomerular activation patterns similar to WT mice and matched WT mice target detection for known background odors. However, Cntnap2-/- mice performance fell almost to chance levels in the presence of novel backgrounds. Our findings suggest that mice use a robust algorithm for detecting odors in novel environments and this computation is impaired in Cntnap2-/- mice.


Neurodevelopmental malformations of the cerebellum and neocortex in the Shank3 and Cntnap2 mouse models of autism

September 2021

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33 Reads

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5 Citations

Neuroscience Letters

There are many mouse models of autism with broad use in neuroscience research. Genetic background can be a major contributor to the phenotype observed in any mouse model of disease, including genetic models of autism. C57BL/6 mice display spontaneous glio-neuronal heterotopia in the cerebellar vermis and neocortex which may also exist in mouse models of autism created on this background. In the present report, we document the presence of cerebellar and neocortical heterotopia in heterozygous and KO Shank3 and Cntnap2 mice which are due to the C57BL/6 genotype and discuss the role these malformations may play in research using these genetic models of autism.


Odor identification in novel olfactory environments is selectively impaired in a mouse model of autism

September 2020

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136 Reads

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1 Citation

Aversion to novel stimuli in autism affects quality of life. We developed a behavioral paradigm to study the effect of novel background odors on odor discrimination in mouse models of autism. We trained wild type mice to discriminate target odors in known background odors. When tested, mice could discriminate known targets in novel background odors, a task similar to the visual CAPTCHA used to distinguish humans from computers. Using glomerular imaging data, we showed that WT mice used an algorithm that required less training data than a linear classifier or nearest neighbor classifier. The Cntnap2 −/− mouse model of autism matched wild type mice performance in the presence of known backgrounds, but performance fell almost to chance levels in the presence of novel backgrounds. Wild-type mice use a robust algorithm for detecting odors in novel environments and this computation is selectively affected in a mouse model of autism.


Figure 2: Earlier date of the start of vaccination reduces the mortality rate. Left panel correspond to upper middle income and high income countries with current universal BCG vaccination policy. The right panel correspond to countries that do not have a current universal vaccination policy.
Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study

March 2020

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72,685 Reads

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466 Citations

COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID-19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guerin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.


Citations (12)


... This result indicates that novel odors might not only be aversive by themselves, but they negatively interfere in the detection of simultaneously present odors. Similar results (see Figure 1) were reported for the Shank3-deficient mice [60]. ...

Reference:

Role of Odor Novelty on Olfactory Issues in Autism Spectrum Disorder
Haploinsufficiency of Shank3 in Mice Selectively Impairs Target Odor Recognition in Novel Background Odors

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

... The major task of any sensory system is to precisely represent external and/or internal stimuli in the brain. For the olfactory system, this involves detecting chemical molecules called odorants using the receptors in the nose and transmitting the processed neural signals to the central olfactory regions of the brain (Ackels et al., 2021;Li et al., 2023;Verhagen et al., 2023). Thus, to study how the olfactory system works, we need to address two major issues: (1) how the receptors transduce different chemical stimuli to electrical neural signals; and (2) how the olfactory centers accurately encode these neural signals for olfactory Review https://doi.org/10.1631/jzus.B2400051 perception. ...

Robust odor identification in novel olfactory environments in mice

... However, further studies are needed to clarify if reduced expression of Rpl3 affects protein synthesis by altering ribosomal assembly and/or by affecting the speed and accuracy of translation. Although we did not nd a change in protein synthesis in the hippocampus, other studies have shown molecular and functional changes in the hippocampus and other brain areas of Shank3 KO mice (53,54,55), emphasizing the importance of better characterizing brain region-speci c mechanisms affected by Shank3 deletion. ...

Neurodevelopmental malformations of the cerebellum and neocortex in the Shank3 and Cntnap2 mouse models of autism
  • Citing Article
  • September 2021

Neuroscience Letters

... Various epidemiological studies found that BCG vaccination is also linked with the reduction of mortality rate in neonates and the reduction of respiratory diseases in elderly people. Recent studies proposed the important relation of BCG immunization with the occurrence, development of the disease, and also mortality due to coronavirus [56]. Many researchers suggested that countries without the global programs for vaccination of BCG have been affected very severely as compared with the countries with the use of the BCG vaccines in neonates. ...

Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study

... Undergraduate neuroscience education has experienced rapid growth over the past 2 decades, with recent studies showing an increase from 90 schools offering a neuroscience major in 2006 to 221 during the 2017-2018 academic year (Ramirez, 2020;Rochon et al., 2019). Interestingly, this growth does not always align with the presence of specific neuroscience departments, as 70% of institutions offering a neuroscience major lack a dedicated department (Pinard-Welyczko et al., 2017). ...

Quantitative Indicators of Continued Growth in Undergraduate Neuroscience Education in the US
  • Citing Article
  • December 2019

Journal of Undergraduate Neuroscience Education

... In primates and humans, past work suggested that this may be supported by two essential features of neocortex: the highly recurrent architecture of cortical networks [1], and an organization of different cortical areas into a temporal processing hierarchy [2,3,4]. It was found that early sensory areas specialize on fast processing of sensory inputs [5,6,7], whereas higher (transmodal) areas perform temporal processing with long timescales -combining new information with past information that is maintained over extended periods [8,9]. This hierarchy is reflected by an increase in the intrinsic timescale of neural activity, as measured by the decay rate of autocorrelation [4,10,11,12]. ...

Millisecond-scale differences in neural activity in auditory cortex can drive decisions

Nature Precedings

... The brain processes information and coordinates behavioral sequences over a wide range of timescales [1][2][3] . While sensory inputs can be processed as fast as tens of milliseconds [4][5][6][7] , cognitive processes such as decision-making or working memory require integrating information over slower timescales from hundreds of milliseconds to minutes [8][9][10] . These differences are paralleled by the timescales of intrinsic fluctuations in neural activity across the hierarchy of cortical areas. ...

Millisecond-scale differences in neural activity in auditory cortex can drive decisions
  • Citing Article
  • September 2008

Nature Precedings

... From a theoretical perspective, it has been posited that top-down signals can direct the lower brain area to suppress response to expected inputs or to inputs that have already been recognized by the higher brain area [8][9][10][11] and to transmit predominantly information about unexpected or unexplained inputs and the error in the prediction of the inputs [12], focusing on task-relevant information. Such specificity in the processing requires that the top-down projections be precisely targeted [10,[13][14][15][16]. The mechanisms that are at work in the formation of these specific connectivities are, however, not well understood. ...

Robust method for finding sparse solutions to linear inverse problems using an L2 regularization
  • Citing Article
  • January 2017

... Within this conceptual framework, cortical feedback has been proposed to support key computations. These range from extracting fine stimulus features 11,12 to learning associations 13,14 and generating sensorimotor predictions 13,15-23 , to modifying and executing motor actions in accordance with behaviorally relevant goals 11,12,15,16,20,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] . While feedback from deeper brain regions reformats visual, auditory, and somatosensory neural representations to enable the differential evaluation of the same sensory inputs 11,24 , the degree to which this is the case for olfactory processing has been less scrutinized 13,16,32,39 . ...

Cortical Feedback Decorrelates Olfactory Bulb Output in Awake Mice
  • Citing Article
  • June 2015

Neuron

... In contrast, Lasso (Tibshirani, 1996), a deconvolution method, could perform well above chance for odor recognition in the presence of novel background odors using WT and Cntnap2 -/À glomerular data (Li et al., 2023). The Lasso deconvolution determines the combination of odors from a large dictionary that could account for observed patterns of glomerular activation produced by a mixture, which is a method that has been proposed as being implemented by the nervous system (Koulakov and Rinberg, 2011;Grabska-Barwi nska et al., 2017;Li and Hertz, 2000;Otazu and Leibold, 2011). The large dictionary reflects all the odors that are known to the animal. ...

A Corticothalamic Circuit Model for Sound Identification in Complex Scenes