Arc expression identifies the lateral amygdala fear memory trace

Memories are encoded within sparsely distributed neuronal ensembles. However, the defining cellular properties of neurons within a memory trace remain incompletely understood. Using a fluorescence-based Arc reporter, we were able to visually identify the distinct subset of lateral amygdala (LA) neurons activated during auditory fear conditioning. We found that Arc-expressing neurons have enhanced intrinsic excitability and are preferentially recruited into newly encoded memory traces. Furthermore, synaptic potentiation of thalamic inputs to the LA during fear conditioning is learning-specific, postsynaptically mediated and highly localized to Arc-expressing neurons. Taken together, our findings validate the immediate-early gene Arc as a molecular marker for the LA neuronal ensemble recruited during fear learning. Moreover, these results establish a model of fear memory formation in which intrinsic excitability determines neuronal selection, whereas learning-related encoding is governed by synaptic plasticity

Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models

RASopathies, characterized by germline mutations in genes encoding proteins of the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest themselves with a varying severity of intellectual disability. However, it is unclear to what extent they share the same downstream pathophysiology that underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy caused by activating mutations in the HRAS gene. Here we investigated the mechanisms underlying the cognitive deficits of HRas G12V/G12V mice. HRas G12V/G12V mice showed robust upregulation of ERK signaling, neuronal hypertrophy, increased brain volume, spatial learning deficits, and impaired mGluR-dependent long-term depression (LTD). In contrast, long-term potentiation (LTP), which is affected in other RASopathy mouse models was unaffected. Treatment with lovastatin, a HMG-CoA-Reductase inhibitor which has been shown to rescue the behavioral phenotypes of mouse models of NF1 and Noonan syndrome, was unable to restore ERK signaling and the cognitive deficits of HRas G12V/G12V mice. Administration of a potent mitogen-activated protein kinase (MEK) inhibitor rescued the ERK upregulation and the mGluR-LTD deficit of HRas G12V/G12V mice, but failed to rescue the cognitive deficits. Taken together, this study indicates that the fundamental molecular and cellular mechanisms underlying the cognitive aspects of different RASopathies are remarkably distinct, and may require disease specific treatments

COMPARAÇÃO DE METODOLOGIAS DE DETERMINAÇÃO DO COEFICIENTE DE DISPERSÃO PARA O CLORETO DE CÁLCIO EM UM LATOSSOLO VERMELHO-AMARELO

RESUMO Com o objetivo de se comparar os métodos de ajuste gráfico e a regressão não-linear na determinação do coeficiente de dispersão, montaram-se três colunas de solo, através das quais se fez passar uma solução deslocadora de cloreto de cálcio (CaCl2), o que permitiu a obtenção dos pontos da curva de eluição. Para efeito de comparação das curvas de eluição ajustadas à experimental, empregaram-se as soluções analíticas das equações diferenciais para a dispersão longitudinal, dispersão para um pulso, difusivo-convectivo e geral do transporte de solutos. Os valores dos coeficientes de dispersão obtidos pelos métodos empregados mostraram que o ajuste gráfico, quando bem empregado, é uma alternativa quando não se dispõe de recursos computacionais para usar o ajuste através de regressão não-linear. As soluções analíticas descrevem com perfeição a curva de eluição, desde que se conheça o coeficiente de dispersão