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1.
Neuron ; 110(20): 3374-3388.e8, 2022 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-36041433

RESUMEN

Individual memories are often linked so that the recall of one triggers the recall of another. For example, contextual memories acquired close in time can be linked, and this is known to depend on a temporary increase in excitability that drives the overlap between dorsal CA1 (dCA1) hippocampal ensembles that encode the linked memories. Here, we show that locus coeruleus (LC) cells projecting to dCA1 have a key permissive role in contextual memory linking, without affecting contextual memory formation, and that this effect is mediated by dopamine. Additionally, we found that LC-to-dCA1-projecting neurons modulate the excitability of dCA1 neurons and the extent of overlap between dCA1 memory ensembles as well as the stability of coactivity patterns within these ensembles. This discovery of a neuromodulatory system that specifically affects memory linking without affecting memory formation reveals a fundamental separation between the brain mechanisms modulating these two distinct processes.


Asunto(s)
Dopamina , Locus Coeruleus , Locus Coeruleus/fisiología , Dopamina/fisiología , Memoria/fisiología , Hipocampo/fisiología , Neuronas/fisiología
2.
Nature ; 606(7912): 146-152, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35614219

RESUMEN

Real-world memories are formed in a particular context and are often not acquired or recalled in isolation1-5. Time is a key variable in the organization of memories, as events that are experienced close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not1-4. How the brain segregates events that are temporally distinct is unclear. Here we show that a delayed (12-24 h) increase in the expression of C-C chemokine receptor type 5 (CCR5)-an immune receptor that is well known as a co-receptor for HIV infection6,7-after the formation of a contextual memory determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed expression of CCR5 in mouse dorsal CA1 neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dorsal CA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, and therefore closes the temporal window for memory linking. Our findings also show that an age-related increase in the neuronal expression of CCR5 and its ligand CCL5 leads to impairments in memory linking in aged mice, which could be reversed with a Ccr5 knockout and a drug approved by the US Food and Drug Administration (FDA) that inhibits this receptor, a result with clinical implications. Altogether, the findings reported here provide insights into the molecular and cellular mechanisms that shape the temporal window for memory linking.


Asunto(s)
Región CA1 Hipocampal , Memoria , Neuronas , Receptores CCR5 , Animales , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/fisiología , Memoria/fisiología , Recuerdo Mental/fisiología , Ratones , Neuronas/metabolismo , Receptores CCR5/deficiencia , Receptores CCR5/genética , Receptores CCR5/metabolismo , Factores de Tiempo
3.
Mol Brain ; 15(1): 7, 2022 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983613

RESUMEN

Systems neuroscience is focused on how ensemble properties in the brain, such as the activity of neuronal circuits, gives rise to internal brain states and behavior. Many of the studies in this field have traditionally involved electrophysiological recordings and computational approaches that attempt to decode how the brain transforms inputs into functional outputs. More recently, systems neuroscience has received an infusion of approaches and techniques that allow the manipulation (e.g., optogenetics, chemogenetics) and imaging (e.g., two-photon imaging, head mounted fluorescent microscopes) of neurons, neurocircuits, their inputs and outputs. Here, we will review novel approaches that allow the manipulation and imaging of specific molecular mechanisms in specific cells (not just neurons), cell ensembles and brain regions. These molecular approaches, with the specificity and temporal resolution appropriate for systems studies, promise to infuse the field with novel ideas, emphases and directions, and are motivating the emergence of a molecularly oriented systems neuroscience, a new discipline that studies how the spatial and temporal patterns of molecular systems modulate circuits and brain networks, and consequently shape the properties of brain states and behavior.


Asunto(s)
Neurociencias , Optogenética , Encéfalo/fisiología , Fenómenos Electrofisiológicos , Neuronas/fisiología , Optogenética/métodos
4.
Cell Rep ; 37(2): 109805, 2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34644573

RESUMEN

Fragile X syndrome (FXS), a commonly inherited form of autism and intellectual disability, is associated with emotional symptoms that implicate dysfunction of the amygdala. However, current understanding of the pathogenesis of the disease is based primarily on studies in the hippocampus and neocortex, where FXS defects have been corrected by inhibiting group I metabotropic glutamate receptors (mGluRs). Here, we observe that activation, rather than inhibition, of mGluRs in the basolateral amygdala reverses impairments in a rat model of FXS. FXS rats exhibit deficient recall of auditory conditioned fear, which is accompanied by a range of in vitro and in vivo deficits in synaptic transmission and plasticity. We find presynaptic mGluR5 in the amygdala, activation of which reverses deficient synaptic transmission and plasticity, thereby restoring normal fear learning in FXS rats. This highlights the importance of modifying the prevailing mGluR-based framework for therapeutic strategies to include circuit-specific differences in FXS pathophysiology.


Asunto(s)
Complejo Nuclear Basolateral/fisiopatología , Conducta Animal , Miedo , Síndrome del Cromosoma X Frágil/fisiopatología , Recuerdo Mental , Plasticidad Neuronal , Transmisión Sináptica , Animales , Complejo Nuclear Basolateral/metabolismo , Modelos Animales de Enfermedad , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/psicología , Masculino , Ratas Sprague-Dawley , Ratas Transgénicas , Receptor del Glutamato Metabotropico 5/metabolismo
5.
CBE Life Sci Educ ; 18(3): ar35, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31397651

RESUMEN

Gender gaps in exam scores or final grades are common in introductory college science and engineering classrooms, with women underperforming relative to men with the same admission test scores or college grade point averages. After failing to close a historically documented gender gap in a large introductory biology course using interventions targeted at training a growth mindset, we implemented interventions designed to reduce student test anxiety. We combined evidence-based exercises based on expressive writing and on reappraising physiological arousal. We also used a valid measure to quantify test anxiety at the start and end of the course. This instrument measures an individual's self-declared or perceived test anxiety-also called trait anxiety-but not the immediate or "state" anxiety experienced during an actual exam. Consistent with previous reports in the literature, we found that women in this population declared much higher test anxiety than men and that students who declared higher test anxiety had lower exam scores than students who declared lower test anxiety. Although the test anxiety interventions had no impact on the level of self-declared trait anxiety, they did significantly increase student exam performance. The treatment benefits occurred in both men and women. These data suggest that 1) a combination of interventions based on expressive writing and reappraising physiological arousal can be a relatively easy manner to boost exam performance in a large-enrollment science, technology, engineering, and mathematics (STEM) course and encourage emotion regulation; 2) women are more willing than men to declare that they are anxious about exams, but men and women may actually experience the same level of anxiety during the exam itself; and 3) women are underperforming in STEM courses for reasons other than gender-based differences in mindset or test anxiety.


Asunto(s)
Ansiedad/psicología , Curriculum , Evaluación Educacional , Ingeniería/educación , Matemática/educación , Ciencia/educación , Estudiantes/psicología , Tecnología/educación , Femenino , Humanos , Masculino , Factores Sexuales , Universidades , Escritura
6.
Elife ; 62017 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-28555566

RESUMEN

Although mGluR5-antagonists prevent fear and anxiety, little is known about how the same receptor in the amygdala gives rise to both. Combining in vitro and in vivo activation of mGluR5 in rats, we identify specific changes in intrinsic excitability and synaptic plasticity in basolateral amygdala neurons that give rise to temporally distinct and mutually exclusive effects on fear-related behaviors. The immediate impact of mGluR5 activation is to produce anxiety manifested as indiscriminate fear of both tone and context. Surprisingly, this state does not interfere with the proper encoding of tone-shock associations that eventually lead to enhanced cue-specific fear. These results provide a new framework for dissecting the functional impact of amygdalar mGluR-plasticity on fear versus anxiety in health and disease.


Asunto(s)
Amígdala del Cerebelo/fisiología , Ansiedad , Miedo , Receptores de Ácido Kaínico/agonistas , Animales , Conducta Animal , Ratas
7.
Rev Bras Enferm ; 69(1): 64-70, 2016.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-26871218

RESUMEN

OBJECTIVE: to evaluate the quality of life of visually impaired using WHOQOL-100. METHOD: exploratory, descriptive, and quantitative study, performed between April and May 2013 with 20 visually impaired of the Blind Association of Ceará, through interviews. RESULTS: the analysis showed that males predominated (80%), 41-55 years (40%), students (50%) and personal income than the minimum wage (70%). Participants were self-rated with good quality of life (68.75%). The facets with the highest rates were personal relationships (74.06%), sexual activity (66.88%) and spirituality/religion/personal beliefs (65%). With lower rates were financial (43.44%), physical environment: pollution/noise/traffic/climate (46.88%), physical security and protection (37.19%), transport (35.63%) and medication or treatment dependency (8.25%). CONCLUSION: these results reflect the importance of the nurse to perform health education actions promoting the empowerment, autonomy and guaranteed of access in society for this clientele.


Asunto(s)
Calidad de Vida , Espiritualidad , Trastornos de la Visión/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Religión
8.
Rev. bras. enferm ; 69(1): 72-78, jan.-fev. 2016. tab, graf
Artículo en Inglés | LILACS, BDENF - Enfermería | ID: lil-771972

RESUMEN

RESUMO Objetivo: avaliar a qualidade de vida de deficientes visuais utilizando WHOQOL-100. Método: estudo exploratório, descritivo e quantitativo, realizado entre abril e maio de 2013 com 20 deficientes visuais da Associação de Cegos do Estado do Ceará, por meio de entrevista. Resultados: a análise mostrou que predominaram sexo masculino (80%), 41 a 55 anos (40%), estudantes (50%) e renda pessoal de até um salário mínimo (70%). Os participantes se autoavaliaram com boa qualidade de vida (68,75%). As facetas com maiores índices foram relações pessoais (74,06%), atividade sexual (66,88%) e espiritualidade/ religião/ crenças pessoais (65%). Com menores índices foram recursos financeiros (43,44%), ambiente físico: poluição/ ruído/ trânsito/ clima (46,88%), segurança física e proteção (37,19%), transporte (35,63%) e dependência de medicação ou de tratamentos (8,25%). Conclusão: esses resultados refletem a importância do enfermeiro em realizar ações de educação em saúde promovendo o empoderamento, autonomia e garantia de acesso na sociedade para esta clientela.


RESUMEN Objetivo: evaluar la calidad de vida de deficientes visuales usando WHOQOL-100. Método: estudio exploratorio, descriptivo y cuantitativo, realizado entre abril y mayo de 2013, con 20 deficientes visuales de la Asociación de Ciegos de Ceará, a través de entrevistas. Resultados: el análisis mostró que el sexo masculino predomina (80%), 41 a 55 anos (40%), estudiantes (50%) y con ingresos personales de hasta un salario mínimo (70%). Los participantes se autoevaluaron con buena calidad de vida (68,75%). Las facetas con mayores tasas fueron relaciones personales (74,06%), la actividad sexual (66,88%) y la espiritualidad/ religión/ creencias personales (65%). Con menores tasas fueron recursos financieros (43,44%), ambiente físico: la contaminación/ruido/ tráfico/clima (46,88%), la seguridad física y la protección (37,19%), el transporte (35,63%) y la dependencia a medicamentos o tratamientos (8,25%). Conclusión: estos resultados reflejan la importancia de la enfermería para realizar acciones de educación para la salud que promueven el empoderamiento, la autonomía y la garantía de acceso en la sociedad para esta clientela.


ABSTRACT Objective: to evaluate the quality of life of visually impaired using WHOQOL-100. Method: exploratory, descriptive, and quantitative study, performed between April and May 2013 with 20 visually impaired of the Blind Association of Ceará, through interviews. Results: the analysis showed that males predominated (80%), 41-55 years (40%), students (50%) and personal income than the minimum wage (70%). Participants were self-rated with good quality of life (68.75%). The facets with the highest rates were personal relationships (74.06%), sexual activity (66.88%) and spirituality/religion/personal beliefs (65%). With lower rates were financial (43.44%), physical environment: pollution/noise/traffic/climate (46.88%), physical security and protection (37.19%), transport (35.63%) and medication or treatment dependency (8.25%). Conclusion: these results reflect the importance of the nurse to perform health education actions promoting the empowerment, autonomy and guaranteed of access in society for this clientele.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Calidad de Vida , Trastornos de la Visión/psicología , Espiritualidad , Religión , Persona de Mediana Edad
9.
Int J Offender Ther Comp Criminol ; 52(3): 311-29, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17717333

RESUMEN

The incarceration of young people is a growing national problem. Key correlates of incarceration among American youth include mental health problems, substance use, and delinquency. The present study uses a statewide sample of incarcerated youth to examine racial differences in African American and Caucasian juvenile offenders' outcomes related to mental health, substance use, and delinquency. The data indicate that relative to Caucasian offenders, African American offenders report lower levels of mental health problems and substance use but higher levels of delinquent behavior such as violence, weapon carrying, and gang fighting. The data further reveal that African American offenders are more likely than Caucasian offenders to be victims of violence and to experience traumatic events such as witnessing injury and death. Recognition of these patterns may help to improve postrelease services by tailoring or adapting preexisting programs to patterns of risk factors and their relative magnitudes of effect.


Asunto(s)
Población Negra/estadística & datos numéricos , Prisioneros , Población Blanca/estadística & datos numéricos , Adolescente , Femenino , Humanos , Delincuencia Juvenil/estadística & datos numéricos , Masculino , Trastornos Mentales/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Estados Unidos
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