- Assistant Professor, Psychology
- Assistant Professor, Neurology
- Assistant Professor, Evelyn F Mcknight Brain Institute
- Assistant Professor, Neuroscience - GIDP
- Assistant Professor, BIO5 Institute
Fabian Fernandez, Ph.D., is an Assistant Professor of Psychology and Neurology, and a Fellow with the BIO5 Institute at the University of Arizona (UA). Dr. Fernandez earned his B.S. in a self-tailored interdisciplinary program in Neurobiological Science from the University of Florida, Gainesville, in 2002, and a Ph.D. in Neurosciences from Stanford University in 2008. While at Stanford, he devised the first hypothesis based pharmacological treatment for intellectual disabilities accompanying Down syndrome and worked with a collaborative team to define the memory problems associated with chronic circadian dysrhythmia. Fabian held positions in industry and at Johns Hopkins University as a research affiliate before joining the UA faculty in 2015.
- Ph.D. Neurosciences
- Stanford University, Palo Alto, California, United States
- Pharmacotherapy for Intellectual Disabilities Associated with Down Syndrome: Work in a Mouse Model
- B.S. IDS - Neurobiological Sciences
- University of Florida, Gainesville, Florida, United States
- Nociceptin/orphanin FQ increases anxiety-related behavior and circulating levels of corticosterone during neophobic tests of anxiety.
- BIO5 Fellow
- University of Arizona, BIO5 Institute, Fall 2015
- Bisgrove Scholar
- Science Foundation Arizona, Fall 2015
- Postdoctoral Fellowship
- La Fondation Jerome-Lejeune, Fall 2007
- Ruth L. Kirschstein NRSA Research Service Award
- National Institutes of Health, Spring 2007
- NSF Predoctoral Fellowship
- National Science Foundation, Fall 2003
As a UA faculty, Dr. Fernandez’s work focuses on circadian timekeeping, an ability that allows us to maintain a close relationship between the inner workings of our mind to the natural schedule of day and night produced by the earth's rotation about its axis. The eye uses a photoreceptor system to process circadian time that is independent of the one it uses for image perception. This system extends from the back of the retina directly to where the brain’s internal clock is located and reacts to the appearance of light presented at different points during the evening. How the brain’s clock ticks in response to illumination of the eye is not well understood. Dr. Fernandez’s research is determining what characteristics of light most influence the brain’s timekeeping ability. With data he is systematically collecting, he will develop the world’s first programming language for how to strategically deliver photic information to normalize the clock's operation when it has weakened. His ultimate goal will be to embody this programming language in a small medical device that can be activated to strengthen circadian rhythms and cognition when a person is asleep. Memory loss occurs during normal aging, is one of the earliest features of cognitive, age- related disease, and is itself presaged by fragmentation of a person’s daily schedule of activity. By augmenting circadian rhythmicity with the medical device—by orienting an individual's cadence so that they are awake during the day and at rest during the evening—Dr. Fernandez hopes to prolong the time the people of Arizona can thrive as they enter the mature stages of life.
Honors ThesisPSIO 498H (Spring 2021)
Sleep + Sleep DisordersPSY 478 (Spring 2021)
Directed ResearchPSYS 492 (Fall 2020)
DissertationNRSC 920 (Fall 2020)
ResearchPSY 900 (Fall 2020)
Directed ResearchPSYS 492 (Summer I 2020)
ResearchNRSC 900 (Spring 2020)
ResearchPSY 900 (Spring 2020)
Sleep + Sleep DisordersPSY 478 (Spring 2020)
Sleep + Sleep DisordersPSY 578 (Spring 2020)
ThesisPSY 910 (Spring 2020)
Master's ReportPSY 909 (Fall 2019)
ResearchNRSC 900 (Fall 2019)
Cognitive PsychologyPSY 596F (Spring 2019)
Honors ThesisNSCS 498H (Spring 2019)
Independent StudyPSIO 499 (Spring 2019)
ResearchNRSC 900 (Spring 2019)
Directed ResearchPSIO 492 (Fall 2018)
Honors ThesisNSCS 498H (Fall 2018)
Independent StudyPSY 499 (Fall 2018)
ResearchNRSC 900 (Fall 2018)
ResearchPSY 900 (Fall 2018)
Directed ResearchPSIO 492 (Spring 2018)
Honors ThesisNSCS 498H (Spring 2018)
ResearchNRSC 900 (Spring 2018)
Sleep + Sleep DisordersPSY 478 (Spring 2018)
Sleep + Sleep DisordersPSY 578 (Spring 2018)
Directed ResearchPSIO 492 (Fall 2017)
Honors ThesisNSCS 498H (Fall 2017)
ResearchNRSC 900 (Fall 2017)
Sleep + Sleep DisordersPSY 478 (Spring 2017)
Sleep + Sleep DisordersPSY 578 (Spring 2017)
Directed ResearchPSIO 492 (Summer I 2016)
Honors ThesisNSCS 498H (Spring 2016)
Intro to BiopsychologyPSY 302 (Spring 2016)
- Fernandez, F. (2018). Precision Light for the Treatment of Psychiatric Disorders. Neural Plasticity.
- Clark, C. A., Fernandez, F., Sakhon, S., Spanò, G., & Edgin, J. O. (2017). The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise. Hippocampus, 27(6), 683-691.More infoRecent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and temporal order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts. By contrast, the DS group had difficulty recalling spatial locations when contextual information was salient and recalling the order in which objects were serially presented. Results are consistent with dysfunction of spatial and temporal contextual pattern separation abilities in individuals with DS, mediated by the hippocampus, including the dentate gyrus. Amidst increasing calls to bridge human and animal work, the memory profile demonstrated here in humans with DS is strikingly similar to that of the Ts65Dn mouse model of DS. The study highlights the trisynaptic circuit as a potentially fruitful intervention target to mitigate cognitive impairments associated with DS.
- Fernandez, F., Nyhuis, C. C., Anand, P., Demara, B. I., Ruby, N. F., Spanò, G., Clark, C., & Edgin, J. O. (2017). Young children with Down syndrome show normal development of circadian rhythms, but poor sleep efficiency: a cross-sectional study across the first 60 months of life. Sleep Medicine, 33, 134-144.More infoTo evaluate sleep consolidation and circadian activity rhythms in infants and toddlers with Down syndrome (DS) under light and socially entrained conditions within a familiar setting. Given previous human and animal data suggesting intact circadian regulation of melatonin across the day and night, it was hypothesized that behavioral indices of circadian rhythmicity would likewise be intact in the sample with DS.
- Fernandez, F., Nyhuis, C., Anand, P., Demara, B., Ruby, N. F., Spano, G., Clark, C. A., & Edgin, J. O. (2017). Young children with Down syndrome show normal development of circadian rhythms, but poor sleep efficiency: a cross-sectional study across the first 60 months of life. Sleep medicine, 134-144.
- Lewis, S. A., Negelspach, D. C., Kaladchibachi, S., Cowen, S. L., & Fernandez, F. (2017). Spontaneous alternation: A potential gateway to spatial working memory in Drosophila. Neurobiology of Learning and Memory, 142(Pt B), 230-235.More infoDespite their ubiquity in biomedical research, Drosophila have yet to be widely employed as model organisms in psychology. Many complex human-like behaviors are observed in Drosophila, which exhibit elaborate displays of inter-male aggression and female courtship, self-medication with alcohol in response to stress, and even cultural transmission of social information. Here, we asked whether Drosophila can demonstrate behavioral indices of spatial working memory in a Y-maze, a classic test of memory function and novelty-seeking in rodents. Our data show that Drosophila, like rodents, alternate their visits among the three arms of a Y-maze and spontaneously favor entry into arms they have explored less recently versus ones they have just seen. These findings suggest that Drosophila possess some of the information-seeking and working memory facilities mammals depend on to navigate through space and might be relevant models for understanding human psychological phenomena such as curiosity.
- Lewis, S., Negelspach, D., Kaladchibachi, S., Cowen, S. L., & Fernandez, F. (2017). Spontaneous Alternation: A Gateway to Spatial Working Memory in Drosophila? Learning and Memory. Learning and Memory.
- Ruby, N. F., Fisher, N., Patton, D. F., Paul, M. J., Fernandez, F., & Heller, H. C. (2017). Scheduled feeding restores memory and modulates c-Fos expression in the suprachiasmatic nucleus and septohippocampal complex. Scientific Reports, 7(1), 6755.More infoDisruptions in circadian timing impair spatial memory in humans and rodents. Circadian-arrhythmic Siberian hamsters (Phodopus sungorus) exhibit substantial deficits in spatial working memory as assessed by a spontaneous alternation (SA) task. The present study found that daily scheduled feeding rescued spatial memory deficits in these arrhythmic animals. Improvements in memory persisted for at least 3 weeks after the arrhythmic hamsters were switched back to ad libitum feeding. During ad libitum feeding, locomotor activity resumed its arrhythmic state, but performance on the SA task varied across the day with a peak in daily performance that corresponded to the previous daily window of food anticipation. At the end of scheduled feeding, c-Fos brain mapping revealed differential gene expression in entrained versus arrhythmic hamsters in the suprachiasmatic nucleus (SCN) that paralleled changes in the medial septum and hippocampus, but not in other neural structures. These data show that scheduled feeding can improve cognitive performance when SCN timing has been compromised, possibly by coordinating activity in the SCN and septohippocampal pathway.
- Fernandez, F., & Edgin, J. O. (2016). Pharmacotherapy in Down's syndrome: which way forward?. The Lancet. Neurology, 15(8), 776-7.
- Fernandez, F., & Reeves, R. H. (2015). Assessing cognitive improvement in people with Down syndrome: important considerations for drug-efficacy trials. Handbook of experimental pharmacology, 228, 335-80.More infoExperimental research over just the past decade has raised the possibility that learning deficits connected to Down syndrome (DS) might be effectively managed by medication. In the current chapter, we touch on some of the work that paved the way for these advances and discuss the challenges associated with translating them. In particular, we highlight sources of phenotypic variability in the DS population that are likely to impact performance assessments. Throughout, suggestions are made on how to detect meaningful changes in cognitive-adaptive function in people with DS during drug treatment. The importance of within-subjects evaluation is emphasized.
- Fernandez, F., Lu, D., Ha, P., Costacurta, P., Chavez, R., Heller, H. C., & Ruby, N. F. (2014). Circadian rhythm. Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing. Science (New York, N.Y.), 346(6211), 854-7.More infoChronic circadian dysfunction impairs declarative memory in humans but has little effect in common rodent models of arrhythmia caused by clock gene knockouts or surgical ablation of the suprachiasmatic nucleus (SCN). An important problem overlooked in these translational models is that human dysrhythmia occurs while SCN circuitry is genetically and neurologically intact. Siberian hamsters (Phodopus sungorus) are particularly well suited for translational studies because they can be made arrhythmic by a one-time photic treatment that severely impairs spatial and recognition memory. We found that once animals are made arrhythmic, subsequent SCN ablation completely rescues memory processing. These data suggest that the inhibitory effects of a malfunctioning SCN on cognition require preservation of circuitry between the SCN and downstream targets that are lost when these connections are severed.
- Zampieri, B. L., Fernandez, F., Pearson, J. N., Stasko, M. R., & Costa, A. C. (2014). Ultrasonic vocalizations during male-female interaction in the mouse model of Down syndrome Ts65Dn. Physiology & behavior, 128, 119-25.More infoDown syndrome (DS) is the leading cause of genetically defined intellectual disability. Although speech and language impairments are salient features of this disorder, the nature of these phenotypes and the degree to which they are exacerbated by concomitant oromotor dysfunction and/or hearing deficit are poorly understood. Mouse models like Ts65Dn, the most extensively used DS animal model, have been critical to understanding the genetic and developmental mechanisms that contribute to intellectual disability. In the present study, we characterized the properties of the ultrasonic vocalizations (USVs) emitted by Ts65Dn males during courtship episodes with female partners. USVs emitted by mice in this setting have been proposed to have some basic correlation to human speech. Data were collected and analyzed from 22 Ts65Dn mice and 22 of their euploid littermates. We found that both the minimum and maximum peak frequencies of Ts65Dn calls were lower than those produced by euploid mice, whereas the mean individual duration of "down" and "complex" syllable types was significantly longer. Peak, minimal and maximal, and the fundamental frequencies of short syllables generated by Ts65Dn mice were lower compared to those by euploid mice. Finally, Ts65Dn males made fewer multiple jumps calls during courtship and the mean total duration of their "arc", "u", and "complex" syllables was longer. We discuss the human correlates to these findings, their translational potential, and the limitations of this approach. To our knowledge, this is the first characterization of differences between adult Ts65Dn and euploid control mice with respect to USVs.
- Fernandez, F., & Edgin, J. O. (2013). Poor Sleep as a Precursor to Cognitive Decline in Down Syndrome : A Hypothesis. Journal of Alzheimer's disease & Parkinsonism, 3(2), 124.More infoWe propose that sleep disruption is a lever arm that influences how cognition emerges in development and then declines in response to Alzheimer disease in people with Down syndrome. Addressing sleep disruptions might be an overlooked way to improve cognitive outcomes in this population. This article is a contribution to a Special Issue on Down Syndrome curated by the editors of the Journal of Alzheimer's Disease & Parkinsonism.
- Ruby, N. F., Fernandez, F., Garrett, A., Klima, J., Zhang, P., Sapolsky, R., & Heller, H. C. (2013). Spatial memory and long-term object recognition are impaired by circadian arrhythmia and restored by the GABAAAntagonist pentylenetetrazole. PloS one, 8(8), e72433.More infoPerformance on many memory tests varies across the day and is severely impaired by disruptions in circadian timing. We developed a noninvasive method to permanently eliminate circadian rhythms in Siberian hamsters (Phodopus sungorus) [corrected] so that we could investigate the contribution of the circadian system to learning and memory in animals that are neurologically and genetically intact. Male and female adult hamsters were rendered arrhythmic by a disruptive phase shift protocol that eliminates cycling of clock genes within the suprachiasmatic nucleus (SCN), but preserves sleep architecture. These arrhythmic animals have deficits in spatial working memory and in long-term object recognition memory. In a T-maze, rhythmic control hamsters exhibited spontaneous alternation behavior late in the day and at night, but made random arm choices early in the day. By contrast, arrhythmic animals made only random arm choices at all time points. Control animals readily discriminated novel objects from familiar ones, whereas arrhythmic hamsters could not. Since the SCN is primarily a GABAergic nucleus, we hypothesized that an arrhythmic SCN could interfere with memory by increasing inhibition in hippocampal circuits. To evaluate this possibility, we administered the GABAA antagonist pentylenetetrazole (PTZ; 0.3 or 1.0 mg/kg/day) to arrhythmic hamsters for 10 days, which is a regimen previously shown to produce long-term improvements in hippocampal physiology and behavior in Ts65Dn (Down syndrome) mice. PTZ restored long-term object recognition and spatial working memory for at least 30 days after drug treatment without restoring circadian rhythms. PTZ did not augment memory in control (entrained) animals, but did increase their activity during the memory tests. Our findings support the hypothesis that circadian arrhythmia impairs declarative memory by increasing the relative influence of GABAergic inhibition in the hippocampus.
- Fernandez, F., Torres, V., & Zamorano, P. (2010). An evolutionarily conserved mechanism for presynaptic trapping. Cellular and molecular life sciences : CMLS, 67(11), 1751-4.More infoPresynaptic differentiation takes place over three interrelated acts involving the biogenesis and trafficking of molecular complexes of active zone material, the "trapping" or stabilization of active zone sites, and the subsequent development of mature synapses. Although the identities of proteins involved with establishing presynaptic specializations have been increasingly delineated, the exact functional mechanisms by which the active zone is assembled remain poorly understood. Here, we discuss a theoretical model for how the trapping stage of presynaptic differentiation might occur in developing neurons. We suggest that subsets of active zone proteins containing polyglutamine domains undergo concentration-dependent prion-like conversions as they accumulate at the plasma membrane. This conversion might serve to aggregate the proteins into a singular structure, which is then able to recruit scaffolding agents necessary for regulated synaptic transmission. A brief informatics analysis in support of this 'Q' assembly hypothesis--across commonly used models of synaptogenesis--is presented.
- Ruby, N. F., Fernandez, F., Zhang, P., Klima, J., Heller, H. C., & Garner, C. C. (2010). Circadian locomotor rhythms are normal in Ts65Dn "Down syndrome" mice and unaffected by pentylenetetrazole. Journal of biological rhythms, 25(1), 63-6.More infoTs65Dn mice are used extensively as a model for Down syndrome. Recent studies have reported conflicting evidence as to whether these mice express circadian rhythms. The authors therefore recorded locomotor activity patterns from these animals while they were housed under a standard light-dark cycle, constant darkness (DD), and constant light (LL). Contrary to expectations, Ts65Dn mice had more robust circadian rhythms with slightly shorter periods compared with their wild-type littermates. They also exhibited increased rhythm period and marked activity suppression when moved from DD to LL (i.e., Aschoff's rule). Administration of the GABA(A) antagonist pentylenetetrazole did not influence any of these circadian parameters. Thus, locomotor activity is under strict circadian control in Ts65Dn mice, suggesting that their cognitive deficits and sleep disturbances are not due to dysfunctional circadian timing as proposed previously.
- Torres, V., Barra, L., Garcés, F., Ordenes, K., Leal-Ortiz, S., Garner, C. C., Fernandez, F., & Zamorano, P. (2010). A bicistronic lentiviral vector based on the 1D/2A sequence of foot-and-mouth disease virus expresses proteins stoichiometrically. Journal of biotechnology, 146(3), 138-42.More infoClassic IRES sequences are notorious for exerting biased expression in favor of upstream coding regions when placed into polycistronic vectors. Here, we report the development of a bicistronic lentiviral system based on the 1D/2A sequence from the foot-and-mouth disease virus that is able to maintain tightly balanced control of upstream and downstream protein expression for several days at a stoichiometry very closely approaching 1.0. Our results suggest that the 1D/2A sequence can be optimized in an FUGW lentiviral setting to coordinate expression of multiple polypeptides, presenting a potentially valuable tool to signaling network researchers and to the gene therapy community.
- Fernandez, F., Trinidad, J. C., Blank, M., Feng, D., Burlingame, A. L., & Garner, C. C. (2009). Normal protein composition of synapses in Ts65Dn mice: a mouse model of Down syndrome. Journal of neurochemistry, 110(1), 157-69.More infoDown syndrome (DS) is the most prevalent form of intellectual disability caused by the triplication of approximately 230 genes on chromosome 21. Recent data in Ts65Dn mice, the foremost mouse model of DS, strongly suggest that cognitive impairment in individuals with DS is a consequence of reduced synaptic plasticity because of chronic over-inhibition. It remains unclear however whether changes in plasticity are tied to global molecular changes at synapses, or are due to regional changes in the functional properties of synaptic circuits. One interesting framework for evaluating the activity state of the DS brain comes from in vitro studies showing that chronic pharmacological silencing of neuronal excitability orchestrates stereotyped changes in the protein composition of synaptic junctions. In the present study, we use proteomic strategies to evaluate whether synapses from the Ts65Dn cerebrum carry signatures characteristic of inactive cortical neurons. Our data reveal that synaptic junctions do not exhibit overt alterations in protein composition. Only modest changes in the levels of synaptic proteins and in their phosphorylation are observed. This suggests that subtle changes in the functional properties of specific synaptic circuits rather than large-scale homeostatic shifts in the expression of synaptic molecules contribute to cognitive impairment in people with DS.
- Fernandez, F., & Garner, C. C. (2008). Episodic-like memory in Ts65Dn, a mouse model of Down syndrome. Behavioural brain research, 188(1), 233-7.More infoTs65Dn mice, like individuals with Down syndrome (DS), demonstrate a functional dissociation between explicit and implicit forms of memory, showing selective impairment in explicit or declarative learning tasks. Here, we explored Ts65Dn explicit memory deficits further by evaluating the ability of these mice to assimilate the temporal and spatial contexts under which previously novel objects had been encountered. We found that Ts65Dn mice could in fact form contextual representations of objects over the course of a few hours, contrary to their inability to discriminate object novelty over a more prolonged period of 24h. These results suggest that Ts65Dn mice might have particular difficulties in declarative tasks requiring long-term memory, presenting an especially important putative therapeutic target for pre-clinical and clinical DS research.
- Ruby, N. F., Hwang, C. E., Wessells, C., Fernandez, F., Zhang, P., Sapolsky, R., & Heller, H. C. (2008). Hippocampal-dependent learning requires a functional circadian system. Proceedings of the National Academy of Sciences of the United States of America, 105(40), 15593-8.More infoDecades of studies have shown that eliminating circadian rhythms of mammals does not compromise their health or longevity in the laboratory in any obvious way. These observations have raised questions about the functional significance of the mammalian circadian system, but have been difficult to address for lack of an appropriate animal model. Surgical ablation of the suprachiasmatic nucleus (SCN) and clock gene knockouts eliminate rhythms, but also damage adjacent brain regions or cause developmental effects that may impair cognitive or other physiological functions. We developed a method that avoids these problems and eliminates rhythms by noninvasive means in Siberian hamsters (Phodopus sungorus). The present study evaluated cognitive function in arrhythmic animals by using a hippocampal-dependent learning task. Control hamsters exhibited normal circadian modulation of performance in a delayed novel-object recognition task. By contrast, arrhythmic animals could not discriminate a novel object from a familiar one only 20 or 60 min after training. Memory performance was not related to prior sleep history as sleep manipulations had no effect on performance. The GABA antagonist pentylenetetrazol restored learning without restoring circadian rhythms. We conclude that the circadian system is involved in memory function in a manner that is independent of sleep. Circadian influence on learning may be exerted via cyclic GABA output from the SCN to target sites involved in learning. Arrhythmic hamsters may have failed to perform this task because of chronic inhibitory signaling from the SCN that interfered with the plastic mechanisms that encode learning in the hippocampus.
- Fernandez, F., & Garner, C. C. (2007). Object recognition memory is conserved in Ts1Cje, a mouse model of Down syndrome. Neuroscience letters, 421(2), 137-41.More infoTs1Cje and Ts65Dn are genetic mouse models of Down syndrome (DS). Like individuals with DS, these mice exhibit various hallmarks of hippocampal pathology, and deficits in hippocampal-based, declarative learning and memory tasks. Both spatial navigation and novel object recognition, two prototypical domains of declarative memory function, have been strongly characterized in the Ts65Dn DS model. Indeed, Ts65Dn mice show navigation problems in the Morris water maze, impaired alternation in a T-maze, and deficient working and reference memory in the radial arm maze task. They, likewise, show an inability to detect object novelty over time. In contrast to the Ts65Dn model, hippocampal-dependent cognition has been less well characterized in Ts1Cje. Although Ts1Cje mice have been found to exhibit spatial difficulties in the Morris water maze and reduced spontaneous alternation, their ability to process object-based information has never been examined. Here, we report that Ts1Cje mice perform normally in short-term and long-term novel object recognition tasks. The ability of Ts1Cje mice to detect object novelty, unlike Ts65Dn, may point to differences in the extent of hippocampal pathology in the two DS mouse models.
- Fernandez, F., & Garner, C. C. (2007). Over-inhibition: a model for developmental intellectual disability. Trends in neurosciences, 30(10), 497-503.More infoDevelopmental intellectual disability (DID) is a daunting societal problem. Although tremendous progress has been made in defining the genetic causes of DID, therapeutic strategies remain limited. In particular, there is a marked absence of a unified approach to treating cognitive impairments associated with DID. Here, we suggest that the brain in many DID-related disorders is subject to a basic imbalance in neuronal activity, with an increased contribution of inhibition to neural circuits. This over-inhibition, in turn, is predicted to lead to deficits in synaptic plasticity and learning and memory. We further discuss possibilities for pharmacological intervention in DID, focusing on the concept of drug-induced 'therapeutic neuroadaptation' as a means of stably enhancing constitutive circuit excitability and cognition over time.
- Fernandez, F., Morishita, W., Zuniga, E., Nguyen, J., Blank, M., Malenka, R. C., & Garner, C. C. (2007). Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nature neuroscience, 10(4), 411-3.More infoTs65Dn mice, a model for Down syndrome, have excessive inhibition in the dentate gyrus, a condition that could compromise synaptic plasticity and mnemonic processing. We show that chronic systemic treatment of these mice with GABAA antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation. These results suggest that over-inhibition contributes to intellectual disabilities associated with Down syndrome and that GABAA antagonists may be useful therapeutic agents for this disorder.
- Fernandez, F., Misilmeri, M. A., Felger, J. C., & Devine, D. P. (2004). Nociceptin/orphanin FQ increases anxiety-related behavior and circulating levels of corticosterone during neophobic tests of anxiety. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 29(1), 59-71.More infoIntracranial administration of nociceptin/orphanin FQ (N/OFQ) increases circulating concentrations of adrenocorticotrophic hormone and corticosterone in unstressed rats, and elevates the responsiveness of these hormones during mild stress. Furthermore, N/OFQ and its cognate receptor are both abundant in a variety of limbic nuclei, and stress exposure decreases neuronal N/OFQ content in forebrain neurons. In light of these and other findings, we examined the potential involvement of N/OFQ in regulation of anxiety-related behaviors in rats. In the open field, elevated plus maze, and dark-light neophobic tests, intracerebroventricular N/OFQ (1.0 pmole-1.0 nmole) increased the expression of anxiety-related behaviors. Specifically, N/OFQ increased the latency to enter, decreased the number of entries into, and decreased the time spent in the exposed or brightly lit environments of all three tests. N/OFQ also enhanced thigmotactic responses in the open field test. The effects of diazepam and of the benzodiazepine inverse agonist FG 7142 were also assessed in independent groups of rats. In all three tests, the behavioral effects of N/OFQ resembled the anxiogenic actions of FG 7142, and contrasted with the anxiolytic actions of diazepam. N/OFQ administration also increased circulating concentrations of corticosterone during anxiety testing, in comparison with the concentrations in vehicle-treated controls. We conclude that N/OFQ administration is anxiogenic, and elevates responsiveness of the hypothalamic pituitary-adrenal axis during neophobic tests of anxiety. This supports the possibility that N/OFQ neurotransmission participates in processing of emotionally-salient and stressful stimuli, and suggests that normal functioning of the N/OFQ system may be important in physiological and psychological well-being.
- Fernandez, F. (2016, April). Changes in time perception during aging can impair memory: Is no clock better than a bad clock?. Ninth Annual McKnight Inter-Institutional Meeting (Invited Talk). Tucson, Arizona: The McKnight Brain Research Foundation.
- Fernandez, F. (2016, Fall). Circadian Programming by Light. BIO5 Fellows Series, University of Arizona (Invited Talk)The BIO5 Institute, University of Arizona.
- Fernandez, F. (2016, January). Programming Circadian Rhythms. UA Sleep Research Conference, Inaugural Meeting (Invited Talk). Old Main, University of Arizona, Tucson: UA School of Mind, Brain, and Behavior.More infoDiscussed recent work in my lab concerned with the development of a smart lens to restore circadian health.
- Fernandez, F. (2016, July). Can Broken Clocks Lead to Broken Memories?. 24th Biennial Meeting of the ISSBD/APS (Invited International Talk). Vilnius, Lithuania: International Society for the Study of Behavioural Development and Association of Psychological Science (APS).More infoWill discuss recent findings from my laboratory suggesting circadian links between Down syndrome and Alzheimer's disease.
- Fernandez, F. (2016, May). Dysrhythmia in the SCN Produces Memory Impairment. Basic Medical Sciences Colloquium Series (Invited State Talk). UA Medical Campus, Phoenix, AZ: BMS Seminar Series, Steering Committee.
- Fernandez, F. (2015, June). Circadian Biomarkers of Pathology Progression in Down syndrome. Biennial Meeting, Trisomy 21 Research Society (Invited International Talk). Paris, France: Trisomy 21 Research Society.More infoDelivered an invited talk at the inaugural meeting of the T21 Research Society.
- Fernandez, F. (2015, October). A Vision for how Circadian Rhythms Shape Memory. Psychology Colloquium, University of Arizona (Invited Talk). UA Campus: Department of Psychology, University of Arizona, Tucson.More infoGave an overview of my laboratory's research goals over the next few decades.
- Fernandez, F. (2015, October). Drug Therapy for a Multigene Neurodevelopmental Disorder: Down syndrome as a Case Study. Genetics and Genomics Grand Rounds, University of Arizona (Invited Talk). University of Arizona Cancer Center, Tucson, AZ: UA Genetics Grand Rounds Committee.More infoLectured on the development of one of the first drug therapies for Down syndrome (DS).
- Fernandez, F. (2015, September). Dysrhythmia-related memory impairment: When no clock is better than a bad clock. Neuroscience Community Datablitz, University of Arizona (Invited Talk). Museum of Contemporary Art, Tucson, AZ: Neuroscience Graduate Interdisciplinary Program, Committee on Neuroscience.More infoDelivered a talk discussing my laboratory's latest work on the links between circadian rhythms and memory.
- Fernandez, F. (2014, September). Down Syndrome: Bridging the Animal-Human Divide. Universidad Nacional Autónoma de México, Congress on Intellectual Disabilities (Invited International Talk). Acapulco, México.: Universidad Nacional Autónoma de México and the government of Mexico.More infoDelivered the Closing Keynote of the conference.
- Fernandez, F. (2016, November). Influence of schizophrenia-associated gene Egr3 on circadian rhythms in mice. Society for Neuroscience Abstracts. San Diego, CA: Society for Neuroscience.
- Fernandez, F. (2014, August). The Truth About Down Syndrome. New York Times. http://www.nytimes.com/2014/08/29/opinion/the-truth-about-down-syndrome.html?_r=0