Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast is widely used for probing brain activity, but its relationship to underlying neural activity remains elusive. Here, we combined fMRI with fiber-optic recordings of fluorescent calcium indicator signals to investigate this relationship in rat somatosensory cortex. Electrical forepaw stimulation (1-10 Hz) evoked fast calcium signals of neuronal origin that showed frequency-dependent adaptation. Additionally, slower calcium signals occurred in astrocyte networks, as verified by astrocyte-specific staining and two-photon microscopy. Without apparent glia activation, we could predict BOLD responses well from simultaneously recorded fiber-optic signals, assuming an impulse response function and taking into account neuronal adaptation. In cases with glia activation, we uncovered additional prolonged BOLD signal components. Our findings highlight the complexity of fMRI BOLD signals, involving both neuronal and glial activity. Combined fMRI and fiber-optic recordings should help to clarify cellular mechanisms underlying BOLD signals.
Sensory maps are reshaped by experience. It is unknown how map plasticity occurs in vivo in functionally diverse neuronal populations because activity of the same cells has not been tracked over long time periods. Here we used repeated two-photon imaging of a genetic calcium indicator to measure whisker-evoked responsiveness of the same layer 2/3 neurons in adult mouse barrel cortex over weeks, first with whiskers intact, then during continued trimming of all but one whisker. Across the baseline period, neurons displayed heterogeneous yet stable responsiveness. During sensory deprivation, responses to trimmed whisker stimulation globally decreased, whereas responses to spared whisker stimulation increased for the least active neurons and decreased for the most active neurons. These findings suggest that recruitment of inactive, 'silent' neurons is part of a convergent redistribution of population activity underlying sensory map plasticity. Sensory-driven responsiveness is a key property controlling experience-dependent activity changes in individual neurons.
La-related proteins (LARPs) belong to an evolutionarily conserved family of factors with predicted roles in RNA metabolism. Here, we have analyzed the cellular interactions and function of LARP4B, a thus far uncharacterized member of the LARP family. We show that LARP4B is a cytosolic protein that accumulates upon arsenite treatment in cellular stress granules. Biochemical experiments further uncovered an interaction of LARP4B with the cytosolic poly(A) binding protein 1 (PABPC1) and the receptor for activated C Kinase (RACK1), a component of the 40S ribosomal subunit. Under physiological conditions, LARP4B co-sedimented with polysomes in cellular extracts, suggesting a role in translation. In agreement with this notion, overexpression of LARP4B stimulated protein synthesis, whereas knockdown of the factor by RNA interference impaired translation of a large number of cellular mRNAs. In sum, we identified LARP4B as a stimulatory factor of translation. We speculate that LARP4B exerts its function by bridging mRNA factors of the 39 end with initiating ribosomes.
Neuromodulation by adenosine is of critical importance in many brain regions, but the role of adenosine in olfactory information processing has not been studied so far. We investigated the effects of adenosine on mitral cells, which are projection neurons of the olfactory bulb. Significant expression of A and A receptors was found in mitral cells, as demonstrated by in situ hybridization. Application of adenosine in acute olfactory bulb slices hyperpolarized mitral cells in wild-type but not in adenosine A receptor knockout mice. Adenosine-induced hyperpolarization was mediated by background K currents that were reduced by halothane and bupivacaine, which are known to inhibit two-pore domain K (K2P) channels. In mitral cells, electrical stimulation of axons of olfactory sensory neurons evoked synaptic currents, which can be considered as input signals, while spontaneous firing independent of sensory input can be considered as noise. Synaptic currents were not affected by adenosine, while adenosine reduced spontaneous firing, leading to an increase in the signal-to-noise ratio of mitral cell firing. Our findings demonstrate that A adenosine receptors activate two-pore domain K channels, which increases the signal-to-noise ratio of the input-output relationship in mitral cells and thereby modulates information processing in the olfactory bulb.
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