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1.
Phys Rev Lett ; 128(9): 091302, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35302802

RESUMO

We search for the signature of parity-violating physics in the cosmic microwave background, called cosmic birefringence, using the Planck data release 4. We initially find a birefringence angle of ß=0.30°±0.11° (68% C.L.) for nearly full-sky data. The values of ß decrease as we enlarge the Galactic mask, which can be interpreted as the effect of polarized foreground emission. Two independent ways to model this effect are used to mitigate the systematic impact on ß for different sky fractions. We choose not to assign cosmological significance to the measured value of ß until we improve our knowledge of the foreground polarization.

2.
Diabetologia ; 55(2): 349-57, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22052079

RESUMO

AIMS/HYPOTHESIS: Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-ß), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. METHODS: We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. RESULTS: The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with ß values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with ß values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with ß values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (ß = -0.05; p = 0.01) and CDKN2A/B (ß = -0.05; p = 0.03) with HOMA-ß. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). CONCLUSIONS/INTERPRETATION: We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.


Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo Genético , Adulto , Alelos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/etnologia , Europa (Continente) , Saúde da Família , Feminino , Genótipo , Humanos , Índia , Insulina/sangue , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Locos de Características Quantitativas , Risco , Irmãos , Migrantes
3.
Neurogastroenterol Motil ; 19(9): 761-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17727395

RESUMO

Our goal was to examine the relationship between early life trauma and the development of visceral hypersensitivity in later life in irritable bowel syndrome (IBS). Rat pups underwent neonatal conditioning: (i) paired odour-shock, where odour is a predictable shock signal, (ii) unpaired odour-shock, where odour is an unpredictable shock signal or (iii) control odour-only with odour presentations and handling without shock. At maturity, colorectal sensitivity was measured as a visceromotor behavioural response. In adulthood, colorectal distension (CRD) induced a pressure-dependent increase in the number of abdominal muscle contractions all three experimental groups. However, compared to animals that had received control odour-only presentations in infancy, there was an attenuated response to CRD in animals previously exposed to neonatal predictable shock pups and an exaggerated response in the animals previously exposed to neonatal unpredictable shock. Adult responses to CRD were altered by infant experience with shock trauma. However, depending on the context of that early life trauma, there are major differences between the long-term effects of that early life trauma on colonic sensitivity compared to controls. These results strengthen the link between early life trauma and adult IBS, and suggest that unpredictable trauma is a critical factor for later life disorders.


Assuntos
Hiperalgesia/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Estresse Psicológico/fisiopatologia , Animais , Animais Recém-Nascidos , Condicionamento Clássico , Medo/fisiologia , Feminino , Masculino , Manometria , Odorantes , Ratos , Fatores de Tempo
4.
Transl Psychiatry ; 7(1): e1005, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28094810

RESUMO

Caregiver maltreatment induces vulnerability to later-life psychopathology. Clinical and preclinical evidence suggest changes in prefrontal and limbic circuitry underlie this susceptibility. We examined this question using a rat model of maternal maltreatment and methods translated from humans, resting-state functional magnetic resonance imaging (R-fMRI). Rat pups were reared by mothers provided with insufficient or abundant bedding for nest building from postnatal (PN) days 8 to 12 and underwent behavioral assessments of affect-related behaviors (forced swim, sucrose preference and social interaction) in adolescence (PN45) and early adulthood (PN60). R-fMRI sessions were conducted under light anesthesia at both ages. Offspring reared with insufficient bedding (that is, maltreated) displayed enduring negative affective behaviors. Amygdala-prefrontal cortex (PFC) functional connectivity increased significantly from adolescence to adulthood in controls, but not in maltreated animals. We computed the fractional amplitude of low-frequency fluctuations (fALFF), an index of intrinsic brain activity, and found that fALFF in medial prefrontal cortex and anterior cingulate cortex (MPFC/ACC) increased significantly with age in controls but remained unchanged in maltreated animals during adolescence and adulthood. We used a seed-based analysis to explore changes in functional connectivity between this region and the whole brain. Compared with controls, maltreated animals demonstrated reduced functional connectivity between MPFC/ACC and left caudate/putamen across both ages. Functional connectivity between MPFC/ACC and right caudate/putamen showed a group by age interaction: decreased in controls but increased in maltreated animals. These data suggest that maltreatment induces vulnerability to psychopathology and is associated with differential developmental trajectories of prefrontal and subcortical circuits underlying affect regulation.


Assuntos
Comportamento Animal , Encéfalo/fisiopatologia , Maus-Tratos Infantis , Comportamento Materno , Tonsila do Cerebelo/fisiopatologia , Animais , Animais Recém-Nascidos , Criança , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos Long-Evans
5.
Br J Ophthalmol ; 90(3): 372-7, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16488965

RESUMO

BACKGROUND/AIM: Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study's aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. METHODS: Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform-methanol mixture. Samples were partitioned in a biphasic system and non-lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by micro-capillary reverse phase chromatography and the effluent examined by nano-electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. RESULTS: The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the alpha2-macroglobulin receptor, IgA alpha chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD-SP21 (also termed high affinity IgE receptor beta subunit), and TrkC tyrosine kinase. CONCLUSIONS: These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease.


Assuntos
Proteínas do Olho/metabolismo , Glândulas Tarsais/metabolismo , Adulto , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Masculino , Proteômica/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Lágrimas/química
6.
Transl Psychiatry ; 6(10): e930, 2016 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-27779623

RESUMO

Disrupted social behavior is a core symptom of multiple psychiatric and neurodevelopmental disorders. Many of these disorders are exacerbated by adverse infant experiences, including maltreatment and abuse, which negatively affect amygdala development. Although a link between impaired social behavior, abnormal amygdala function and depressive-like behavior following early adversity has been demonstrated in humans and animal models, the developmental emergence of maltreatment-related social deficits and associated amygdala neural activity are unknown. We used a naturalistic rodent model of maternal maltreatment during a sensitive period, postnatal days 8-12 (PN8-12), which produces social behavior deficits that precede adolescent depressive-like behavior and amygdala dysfunction, to examine social behavior in infancy, periweaning and adolescence. Neural activity in response to the social behavior test was assessed via c-Fos immunohistochemistry at these ages. A separate group of animals was tested for adult depressive-like behavior in the forced swim test. Maltreatment spared infant (PN16-18) social behavior but disrupted periweaning (PN20-22) and adolescent (PN42-48) social behavior. Maltreated rats exhibited blunted neural activation in the amygdala and other areas implicated in social functioning, including the medial prefrontal cortex and nucleus accumbens, at these ages and increased adult depressive-like behavior. These findings may suggest corticolimbic involvement in the emergence of maltreatment-induced social deficits that are linked to adult depressive-like behavior, thereby highlighting potential targets for therapeutic intervention. Understanding how infant experiences influence social behavior and age-specific expression across development may provide insights into basic neural mechanisms of social behaviors and disease-relevant social dysfunction exacerbated by early-life stress.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Acontecimentos que Mudam a Vida , Transtornos do Comportamento Social/fisiopatologia , Fatores Etários , Animais , Feminino , Expressão Gênica/genética , Masculino , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Long-Evans , Desmame
7.
Genes Brain Behav ; 15(1): 144-54, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26534899

RESUMO

Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here, we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups' transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes.


Assuntos
Tonsila do Cerebelo/fisiologia , Aprendizagem por Associação , Desenvolvimento Infantil , Medo , Tonsila do Cerebelo/crescimento & desenvolvimento , Animais , Humanos , Lactente , Neurogênese
8.
J Neurosci ; 19(12): 5131-7, 1999 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10366646

RESUMO

The following experiments determined that the somatosensory whisker system is functional and capable of experience-dependent behavioral plasticity in the neonate before functional maturation of the somatosensory whisker cortex. First, unilateral whisker stimulation caused increased behavioral activity in both postnatal day (P) 3-4 and P8 pups, whereas stimulation-evoked cortical activity (14C 2-deoxyglucose autoradiography) was detectable only in P8 pups. Second, neonatal rat pups are capable of forming associations between whisker stimulation and a reinforcer. A classical conditioning paradigm (P3-P4) showed that the learning groups (paired whisker stimulation-shock or paired whisker stimulation-warm air stream) exhibited significantly higher behavioral responsiveness to whisker stimulation than controls. Finally, stimulus-evoked somatosensory cortical activity during testing [P8; using 14C 2-deoxyglucose (2-DG) autoradiography] was assessed after somatosensory conditioning from P1-P8. No learning-associated differences in stimulus-evoked cortical activity were detected between learning and nonlearning control groups. Together, these experiments demonstrate that the whisker system is functional in neonates and capable of experience-dependent behavioral plasticity. Furthermore, in contrast to adult somatosensory classical conditioning, these data suggest that the cortex is not required for associative somatosensory learning in neonates.


Assuntos
Comportamento Animal/fisiologia , Condicionamento Psicológico/fisiologia , Córtex Somatossensorial/fisiologia , Vibrissas/fisiologia , Animais , Animais Recém-Nascidos , Antimetabólitos/farmacocinética , Aprendizagem por Associação/fisiologia , Desoxiglucose/farmacocinética , Eletrochoque , Feminino , Temperatura Alta , Masculino , Plasticidade Neuronal/fisiologia , Estimulação Física , Ratos , Ratos Long-Evans , Vibrissas/inervação
9.
Neuroscientist ; 10(6): 513-24, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15534037

RESUMO

We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory.


Assuntos
Encéfalo/fisiologia , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Condutos Olfatórios/fisiologia , Animais , Encéfalo/anatomia & histologia , Humanos , Modelos Neurológicos , Condutos Olfatórios/anatomia & histologia , Receptores de Neurotransmissores/fisiologia , Olfato/fisiologia , Transmissão Sináptica/fisiologia
10.
Neuroscience ; 65(3): 757-66, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7609874

RESUMO

The effects of left, right or bilateral depletion of the mesocortical dopamine innervation (medial prefrontal and anterior cingulate) with 6-hydroxydopamine were examined in male Sprague-Dawley rats tested for susceptibility to cold restraint-induced gastric stress pathology. All three types of lesions tended to potentiate the development of stress pathology (i.e. ulceration) in comparison to restrained shams, but only right cortical dopamine depletion produced a highly significant increase. The results support a protective role for mesocortical dopamine in helping the organism cope with stressful situations, and extend previous findings suggesting that dopamine activation in the right cortex is preferentially associated with uncontrollable stress. The right cortex is hypothesized to be at the top of a hierarchy in the processing of such stressful inputs, and endogenous dopaminergic modulation facilitates adaptive responses. Subcortical dopamine terminal regions were also examined for dopamine content and turnover. In addition to depleting cortical dopamine, the three lesion groups showed highly specific alterations in the status of subcortical dopamine systems, compared to either restrained or non-restrained shams. Left brain lesions resulted in significant bilateral increases in amygdala dopamine turnover. Right cortical lesions induced significant bilateral reductions of striatal dopamine content. Bilateral lesions increased dopamine content in the left amygdala and decreased dopamine in the right nucleus accumbens. Also in this group, dopamine turnover was increased in the right nucleus accumbens and decreased in the right amygdala. The data suggest that increases in stress vulnerability induced by cortical lesions may be related, in part, to neurochemical alterations in subcortical structures previously shown to modulate gastric stress pathology. The results also indicate that brain organization is inherently asymmetrical with respect to the regulation of responses to stress, which may be of significance for human psychopathology and its exacerbation by stress.


Assuntos
Córtex Cerebral/fisiologia , Dopamina/metabolismo , Tonsila do Cerebelo/fisiologia , Animais , Corpo Estriado/fisiologia , Masculino , Núcleo Accumbens/fisiologia , Oxidopamina/farmacologia , Ratos , Ratos Sprague-Dawley , Estresse Fisiológico/patologia , Úlcera
11.
Neuroscience ; 83(1): 81-91, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9466400

RESUMO

In the present study, in vivo voltammetry was used to monitor changes in dopamine levels in the left and right medial prefrontal cortex of rats exposed to mild physical and psychological stress. These were 2 min of tail-pinch and 15 min exposure to cat odour, respectively. Fourteen male Long Evans rats with bilateral carbon fibre recording electrodes were tested on four consecutive days, and records obtained in each medial prefrontal cortex for each stressor. A week later, animals underwent a 20 min restraint stress, with plasma samples taken at 0, 20 and 80 min to determine stress-induced corticosterone responses. It was found that dopamine responses to tail-pinch were significantly longer-lasting in the left hemisphere than in the right, while this asymmetry was not present for the dopamine response to cat odour. Stress-induced dopamine increases elicited by the two stressors were significantly correlated only in the right medial prefrontal cortex. Restraint stress-induced increases in plasma corticosterone were positively correlated with dopaminergic responses to tail-pinch, but were only related to dopamine cat odour responses when individual asymmetries favoured the right medial prefrontal cortex. The data suggest that asymmetric mesocortical dopamine activation depends on the type of stress, and that regulation of dopamine responses to both types of stress is most tightly coupled in the right hemisphere. While neuroendocrine and dopaminergic stress responses are positively linked, this relationship is only asymmetrical for the psychological stressor, suggesting a specialized role for right cortical mechanisms in the integration of emotional and physiological responses to stressful situations. A preliminary report of this work was presented at the Society for Neuroscience meeting in Washington DC, November, 1996.


Assuntos
Corticosterona/sangue , Dopamina/metabolismo , Lateralidade Funcional/fisiologia , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/metabolismo , Anfetamina/farmacologia , Animais , Inibidores da Captação de Dopamina/farmacologia , Eletroquímica , Masculino , Córtex Pré-Frontal/anatomia & histologia , Ratos , Comportamento Estereotipado/efeitos dos fármacos
12.
Neuroscience ; 116(1): 285-93, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12535960

RESUMO

In vivo voltammetry was used to study the effects of basolateral amygdala dopamine depletion on stress-induced dopamine release in the nucleus accumbens and medial prefrontal cortex. Male Long-Evans rats received bilateral microinjections of 6-hydroxydopamine or vehicle into the basolateral amygdala. Changes in dopamine signal were monitored in the nucleus accumbens and in the right and left hemispheres of medial prefrontal cortex, in lesioned animals and shams. Animals were subjected to a physical stressor (tail pinch) and a species-typical threat (fox odour); each stressor was presented twice over four consecutive daily sessions. The results indicate that the nucleus accumbens dopamine responses to both stressors are significantly potentiated by dopamine-depleting lesions to basolateral amygdala. In contrast, while the dopamine stress response in the left medial prefrontal cortex did not differ between lesioned animals and shams, the right medial prefrontal cortical dopamine response to tail pinch, but not fox odour stress, was significantly attenuated in lesioned animals. Therefore, basolateral amygdala dopamine depletion had opposite effects on the nucleus accumbens and medial prefrontal cortical dopamine responses to stress, although the effect on the latter is lateralized to the right hemisphere in a stressor-specific manner. These data indicate that stress-induced activation of meso-amygdaloid dopamine exerts an inhibitory influence on the nucleus accumbens dopamine response to stress. They also suggest the possibility that meso-amygdaloid dopamine influences the nucleus accumbens dopamine response to stress indirectly by modulating stress-induced dopamine release in medial prefrontal cortex. These findings add to a growing body of evidence of a preferential involvement of right medial prefrontal cortical dopamine in a wide range of physiological responses to stress.


Assuntos
Tonsila do Cerebelo/metabolismo , Dopamina/metabolismo , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Eletroquímica , Lateralidade Funcional , Masculino , Degeneração Neural/induzido quimicamente , Neurônios/efeitos dos fármacos , Norepinefrina/metabolismo , Oxidopamina , Ratos , Ratos Long-Evans , Estresse Psicológico , Simpatolíticos
13.
Neuroscience ; 83(3): 781-9, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9483561

RESUMO

The present study examined post mortem changes in central dopaminergic terminal regions following acute or chronic treatment regimens with the dopamine D2/D3 receptor agonist quinpirole, a psychomotor stimulant which induces pronounced behavioural sensitization when given chronically. Drug-induced changes in nucleus accumbens, striatum and amygdala were bilateral in nature, while in prefrontal cortex (medial prefrontal and anterior cingulate combined), left and right brain regions responded differentially to quinpirole. Acute drug treatment increased dopamine tissue levels in nucleus accumbens and right prefrontal cortex, while the dopamine metabolite 3,4-dihydroxyphenylacetic acid, was decreased in amygdala. In contrast, sensitization to quinpirole was associated with decreased dopamine levels in left prefrontal cortex, and increases in 3,4-dihydroxyphenylacetic acid levels in subcortical structures, particularly striatum and amygdala. Additionally, the increase in striatal 3,4-dihydroxyphenylacetic acid in chronic quinpirole animals was independent of drug treatment on the final day of injections. In summary, quinpirole induces a variety of simultaneous, regional changes in dopaminergic function, with the sensitized condition being primarily associated with an up-regulation of subcortical dopamine activity. While the nucleus accumbens and striatum play a well known role in motor activation and sensitized behaviour, it is concluded that the amygdala and prefrontal cortex have significant modulatory influences on these processes, with the role of the prefrontal cortex being asymmetrical in nature. Given the suggested relevance of behavioural sensitization to psychopathological states in humans, parallels are drawn between the present data and clinical findings, particularly in relation to obsessive-compulsive disorder.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Agonistas de Dopamina/farmacologia , Dopamina/fisiologia , Quimpirol/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Masculino , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Endogâmicos
14.
Pediatrics ; 87(4): 511-8, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2011429

RESUMO

One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unconditioned stimulus (a stimulus with positive properties). Control babies received only the odor, only the stroking, or the stroking followed by the odor presentation. The next day, all infants, in either the awake or sleep state, were given five 30-second presentations of the odor. Results were analyzed from video tapes scored by an observer unaware of the infants' training condition. The results indicate that only those infants who received the forward pairings of the odor and stroking exhibited conditioned responding (head turning toward the odor) to the citrus odor. The performance of the conditioned response was not affected by the state of the baby during testing, because both awake and sleeping infants exhibited conditioned responses. Furthermore, the expression of the conditioned response was odor specific; a novel floral odor presented during testing did not elicit conditioned responses in the experimental babies. These results suggest that complex associative olfactory learning is seen in newborns within the first 48 hours of life. These baseline findings may serve as normative data against which observation from neonates at risk for neurological sequelae may be compared.


Assuntos
Condicionamento Clássico , Recém-Nascido/psicologia , Olfato/fisiologia , Feminino , Humanos , Masculino , Tato/fisiologia
15.
Behav Neurosci ; 107(2): 254-63, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8484891

RESUMO

Although olfactory associative conditioning in newborn rats produces marked structural and functional changes in the olfactory bulb, recent evidence suggests that extrabulbar circuits must be involved in storing these early memories. The present experiments examined the role of the amygdala complex on early olfactory learning. Bilateral amygdala lesions or sham lesions were performed on Postnatal Day (PN) 5. On PN6, pups were trained in a standard classical conditioning paradigm associating odor with tactile stimulation. Behavioral testing on PN7 revealed that amygdala lesions blocked odor preferences but had no effect on conditioned behavioral activation. Similar sized neocortical lesions did not impair odor preferences. Importantly, amygdala lesion effects on learned odor preferences could be reversed by extensive overtraining. These results suggest that the amygdala complex plays a critical role in modulating associative learning as early as the first postnatal week in the rat.


Assuntos
Envelhecimento/fisiologia , Tonsila do Cerebelo/fisiologia , Aprendizagem por Associação/fisiologia , Condicionamento Clássico/fisiologia , Olfato/fisiologia , Animais , Animais Recém-Nascidos , Nível de Alerta/fisiologia , Mapeamento Encefálico , Dominância Cerebral/fisiologia , Neurônios/fisiologia , Ratos , Ratos Wistar
16.
Behav Neurosci ; 105(2): 307-12, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2043275

RESUMO

Newborn rat pups can learn to either approach or avoid odor cues through associative conditioning. The present results demonstrate that preference conditioning and avoidance conditioning both modify olfactory bulb responses (focal 2-deoxyglucose uptake and mitral-tufted cell single unit responses) to the conditioned odor. Despite opposing behavioral responses to the conditioned odor, however, olfactory bulb neural responses did not detectably differ between learned odor cues signaling approach and those signaling avoidance. Control pups exhibited neither the behavioral nor neural changes. Furthermore, both the behavioral and neural changes to these odor cues could be extinguished. These results suggest that the olfactory bulb in neonates may code learned odor importance, but specific information attached to that importance may require processing in other brain regions.


Assuntos
Aprendizagem por Associação/fisiologia , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Bulbo Olfatório/fisiologia , Olfato/fisiologia , Animais , Animais Recém-Nascidos , Eletrochoque , Extinção Psicológica/fisiologia , Feminino , Fixação Psicológica Instintiva/fisiologia , Masculino , Rememoração Mental/fisiologia , Neurônios/fisiologia , Ratos , Ratos Endogâmicos
17.
Behav Neurosci ; 105(6): 843-9, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1663758

RESUMO

One of the circuits modified by early olfactory learning is in the olfactory bulb. Specifically, response patterns of mitral-tufted cells are modified by associative conditioning during the early postnatal period. In addition, previous work has demonstrated that mitral-tufted cell single units respond to both olfactory conditioned stimuli and rewarding stimulation of the medial forebrain bundle-lateral hypothalamus (MFB-LH). The present study suggests that norepinephrine beta-receptor activation is required for early olfactory learning using MFB-LH stimulation as reward. Propranolol injected before odor-MFB-LH pairings blocks the acquisition of conditioned behavioral responses and their neural correlates to the conditioned odor. Furthermore, propranolol blocks a specific class of the mitral-tufted cell responses to MFB-LH reward stimulation. The relationship of this response to reward and early learning is discussed.


Assuntos
Envelhecimento/fisiologia , Nível de Alerta/fisiologia , Condicionamento Clássico/fisiologia , Motivação , Plasticidade Neuronal/fisiologia , Bulbo Olfatório/fisiologia , Olfato/fisiologia , Animais , Animais Recém-Nascidos/fisiologia , Mapeamento Encefálico , Estimulação Elétrica , Feminino , Região Hipotalâmica Lateral/fisiologia , Masculino , Feixe Prosencefálico Mediano/fisiologia , Neurônios/fisiologia , Norepinefrina/fisiologia , Condutos Olfatórios/fisiologia , Ratos , Ratos Endogâmicos , Recompensa , Transmissão Sináptica/fisiologia
18.
Behav Neurosci ; 108(6): 1053-8, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7893397

RESUMO

Wistar rat pups, aged Postnatal Day 5, were trained in an olfactory associative learning task with citral odor as the conditioned stimulus (CS) and intraoral infusions of milk as the unconditioned stimulus (US). Following a 30-min training session, pups were injected with either the norepinephrine beta-receptor antagonist propranolol or the beta-receptor agonist isoproterenol. Pups were tested 24 hr later for an acquired relative odor preference for the CS. Propranolol injected immediately following training impaired memory for the CS in a dose-dependent manner. This posttraining effect lasted less than 4 hr. Isoproterenol injected immediately after training also impaired memory performance, even at very low doses. These results suggest that posttraining levels of norepinephrine play a critical role in memory consolidation in the newborn, with elevations or decrements in noradrenergic activity resulting in impaired memory.


Assuntos
Envelhecimento/fisiologia , Aprendizagem por Associação/fisiologia , Condicionamento Clássico/fisiologia , Rememoração Mental/fisiologia , Norepinefrina/fisiologia , Animais , Animais Recém-Nascidos , Comportamento Apetitivo/efeitos dos fármacos , Comportamento Apetitivo/fisiologia , Aprendizagem por Associação/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Isoproterenol/farmacologia , Masculino , Rememoração Mental/efeitos dos fármacos , Propranolol/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos/efeitos dos fármacos , Receptores Adrenérgicos/fisiologia , Olfato/efeitos dos fármacos , Olfato/fisiologia
19.
Behav Neurosci ; 114(5): 957-62, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11085610

RESUMO

These experiments examined the sufficiency of pairing an odor with either intrabulbar activation of noradrenergic beta-receptors or pharmacological stimulation of the locus coeruleus to support learned odor preferences in Postnatal Day 6-7 rat pups. The results showed that pups exposed to odor paired with beta-receptor activation limited to the olfactory bulb (isoproterenol, 50 microM) displayed a conditioned approach response on subsequent exposure to that odor. Furthermore, putative stimulation of the locus coeruleus (2 microM idazoxan or 2 mM acetylcholine) paired with odor produced a subsequent preference for that odor. The effects of locus coeruleus stimulation could be blocked by a pretraining injection of the beta-receptor antagonist propranolol (20 mg/kg). Together these results suggest that convergence of odor input with norepinephrine release from the locus coeruleus terminals within the olfactory bulb is sufficient to support olfactory learning.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Isoproterenol/farmacologia , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/metabolismo , Odorantes , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/metabolismo , Receptores Adrenérgicos beta/metabolismo , Olfato/efeitos dos fármacos , Olfato/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Masculino , Ratos , Ratos Long-Evans
20.
Brain Res ; 432(2): 307-11, 1987 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3676845

RESUMO

The expression of a conditioned odor preference and focal uptake of [14C]2-deoxyglucose (2-DG) within the olfactory bulb was assessed in neonatal rat pups that had undergone a single olfactory classical conditioning trial. At 6 days of age, rat pups were simultaneously exposed for 10 min to an odor (peppermint) and to a reinforcing tactile stimulation similar to that received from the dam. Three control groups received only the odor, only the stimulation, or neither of these stimuli. The next day, pups were either assessed for differential olfactory bulb activity using the 2-DG technique or tested for their olfactory preference behavior. Only pups that received simultaneous odor and tactile stimulation exhibited an attraction to the conditioned odor in the two-odor choice test. Furthermore, such pups had greater focal 2-DG uptake in the olfactory bulb glomeruli that were responsive to the odor than pups in all other groups. Thus, the olfactory bulb responds differentially to an odor which has acquired attractive value.


Assuntos
Condicionamento Clássico/fisiologia , Bulbo Olfatório/fisiologia , Olfato/fisiologia , Fatores Etários , Animais , Autorradiografia , Desoxiglucose , Aprendizagem por Discriminação/fisiologia , Feminino , Masculino , Odorantes , Bulbo Olfatório/metabolismo , Ratos , Ratos Endogâmicos
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