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Madruga, B.

Publications and source records attributed to Madruga, B..

2 recordsLinked to original sources

Voltage imaging reveals that hippocampal interneurons tune memory-encoding pyramidal sequences

Hippocampal spiking sequences encode and link behavioral information across time. How inhibition sculpts these sequences remains unknown. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin-expressing interneurons in mice during an odor-cued working memory task, before and after training. During this task, pyramidal odor-specific sequences encode the cue throughout a delay period. In contrast, most interneurons encoded odor delivery, but not odor identity, nor delay time. Population inhibition was stable across days, with constant field turnover, though some cells retained odor-responses for days. At odor onset, a brief, synchronous burst of parvalbumin cells was followed by widespread membrane hyperpolarization and then rebound theta-paced spiking, synchronized across cells. Two-photon calcium imaging revealed that most pyramidal cells were suppressed throughout the odor. Positive pyramidal odor-responses coincided with interneuronal rebound spiking; otherwise, they had weak odor-selectivity. Therefore, inhibition increases the signal-to-noise ratio of cue representations, which is crucial for entraining downstream targets.

neuroscience↗

A positively Tuned Voltage Indicator Reveals Electrical Correlates of Calcium Activity in the Brain

Neuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but calcium imaging is limited in temporal resolution and does not report subthreshold voltage changes. Genetically encoded voltage indicators (GEVIs) offer better temporal resolution and subthreshold sensitivity, but spike detection with fast GEVIs has required specialized imaging equipment. Here, we report the ASAP4 subfamily of genetically encoded voltage indicators (GEVIs) that brighten in response to membrane depolarization, inverting the fluorescence-voltage relationship of previous ASAP GEVIs. Two variants, ASAP4b and ASAP4e, feature 128% and 178% fluorescence increases over 100-mV of depolarization, respectively, facilitating spike detection in single trials in vivo with standard 1 and 2-photon imaging systems. Simultaneous voltage and calcium imaging confirms improved temporal resolution and spike discernment by ASAP4 GEVIs. Thus, positively tuned ASAP4 voltage indicators enable recording of neuronal spiking activity using similar equipment as calcium imaging, while providing higher temporal resolution. One Sentence SummaryUpward ASAPs increase detection capability of GEVIs in vivo.

neuroscience↗