Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo define a mechanism for network oscillations

Theta-gamma network oscillations are thought to represent key reference signals for information processing in neuronal ensembles, but the underlying synaptic mechanisms remain unclear. To address this question, we performed whole-cell (WC) patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials at low frequency, consistent with sparse coding in the dentate gyrus. GCs were exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs exhibited coherence with the field potential predominantly in the theta frequency band, whereas IPSCs showed coherence primarily in the gamma range. Action potentials in GCs were phase locked to network oscillations. Thus, theta-gamma-modulated synaptic currents may provide a framework for sparse temporal coding of information in the dentate gyrus

Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats

The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation

Genetic Evidence for Involvement of Neuronally Expressed S1P1 Receptor in Nociceptor Sensitization and Inflammatory Pain

Sphingosine-1-phosphate (S1P) is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P1 receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P1 receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P1 receptor. Our data show that neuronally expressed S1P1 receptors play a significant role in regulating nociceptor function and that S1P/S1P1 signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation

The multiple faces of RIM

Rab3 interacting molecules (RIMs) are highly enriched in the active zones of presynaptic terminals. It is generally thought that they operate as effectors of the small G protein Rab3. Three recent papers, by Han et al. (this issue of Neuron), Deng et al. (this issue of Neuron), and Kaeser et al. (a recent issue of Cell), shed new light on the functional role of RIM in presynaptic terminals. First, RIM tethers Ca2+ channels to active zones. Second, RIM contributes to priming of synaptic vesicles by interacting with another presynaptic protein, Munc13

Brain-wide 3D light-field imaging of neuronal activity with speckle-enhanced resolution

A major challenge in neuroscience is to sample large-scale neuronal activity at high speed and resolution. While calcium (Ca2+) imaging allows high-resolution optical read-out of neuronal activity, it remains challenging to sample large-scale activity at high speed, as most available imaging microscopes provide a trade-off between speed and the size of the acquisition volume. One promising method that avoids the trade-off between the acquisition rate and volume size is light-field microscopy in which the full 3D profile of an object is imaged simultaneously, thereby offering high speed at the cost of reduced spatial resolution. Here we introduce speckle light-field microscopy (speckle LFM), which utilizes speckle-based structured illumination to enhance spatial resolution. Using speckle LFM we demonstrate brain-wide recording of neuronal activity in larval zebrafish at 10 Hz volume rate and at 1.4 times higher resolution compared to conventional light-field microscopy and with suppressed background fluorescence. In addition to improving resolution of spatial structure, we show that the increased resolution reduces spurious signal crosstalk between neighboring neurons. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen