Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning.

The mechanisms by which astrocytes modulate neural homeostasis, synaptic plasticity, and memory are still poorly explored. Astrocytes form large intercellular networks by gap junction coupling, mainly composed of two gap junction channel proteins, connexin 30 (Cx30) and connexin 43 (Cx43). To circumvent developmental perturbations and to test whether astrocytic gap junction coupling is required for hippocampal neural circuit function and behavior, we generate and study inducible, astrocyte-specific Cx30 and Cx43 double knockouts. Surprisingly, disrupting astrocytic coupling in adult mice results in broad activation of astrocytes and microglia, without obvious signs of pathology. We show that hippocampal CA1 neuron excitability, excitatory synaptic transmission, and long-term potentiation are significantly affected. Moreover, behavioral inspection reveals deficits in sensorimotor performance and a complete lack of spatial learning and memory. Together, our findings establish that astrocytic connexins and an intact astroglial network in the adult brain are vital for neural homeostasis, plasticity, and spatial cognition.

Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits.

Recent investigations of Nogo-A, a well characterized protein inhibitor of neurite outgrowth in the brain, have revealed additional functions including a role in neuropsychiatric disorders such as schizophrenia. Here we examined Nogo-A functions in mouse CA3 hippocampal circuitry. Patch clamp recordings showed that the absence of Nogo-A results in a hyperactive network. In addition, mGlu3 metabotropic glutamate receptors, which exhibit mutations in certain forms of schizophrenia, were downregulated specifically in the CA3 area. Furthermore, Nogo-A-/- mice showed disordered theta oscillations with decreased incidence and frequency, similar to those observed in mGlu3-/- mice. As disruptions in theta rhythmicity are associated with impaired spatial navigation, we tested mice using modified Morris water maze tasks. Mice lacking Nogo-A exhibited altered search strategies, displaying greater dependence on global as opposed to local reference frames. This link between Nogo-A and mGlu3 receptors may provide new insights into mechanisms underlying schizophrenia.

A Sensitive Dynamic and Active Pixel Vision Sensor for Color or Neural Imaging Applications.

Applications requiring detection of small visual contrast require high sensitivity. Event cameras can provide higher dynamic range (DR) and reduce data rate and latency, but most existing event cameras have limited sensitivity. This paper presents the results of a 180-nm Towerjazz CIS process vision sensor called SDAVIS192. It outputs temporal contrast dynamic vision sensor (DVS) events and conventional active pixel sensor frames. The SDAVIS192 improves on previous DAVIS sensors with higher sensitivity for temporal contrast. The temporal contrast thresholds can be set down to 1% for negative changes in logarithmic intensity (OFF events) and down to 3.5% for positive changes (ON events). The achievement is possible through the adoption of an in-pixel preamplification stage. This preamplifier reduces the effective intrascene DR of the sensor (70 dB for OFF and 50 dB for ON), but an automated operating region control allows up to at least 110-dB DR for OFF events. A second contribution of this paper is the development of characterization methodology for measuring DVS event detection thresholds by incorporating a measure of signal-to-noise ratio (SNR). At average SNR of 30 dB, the DVS temporal contrast threshold fixed pattern noise is measured to be 0.3%-0.8% temporal contrast. Results comparing monochrome and RGBW color filter array DVS events are presented. The higher sensitivity of SDAVIS192 make this sensor potentially useful for calcium imaging, as shown in a recording from cultured neurons expressing calcium sensitive green fluorescent protein GCaMP6f.