Biology subjects

Lee, A. K.

Publications and source records attributed to Lee, A. K..

22 records · Page 2Linked to original sources

bioRxiv2020

Robotic Multi-Probe-Single-Actuator Inchworm Neural Microdrive

Electrophysiology is one of the major experimental techniques used in neuroscience. The favorable spatial and temporal resolution as well as the increasingly larger site counts of brain recording electrodes contribute to the popularity and importance of electrophysiology in neuroscience. Such electrodes are typically mechanically placed in the brain to perform acute or chronic freely moving animal measurements. The micro positioners currently used for such tasks employ a single translator per independent probe being placed into the targeted brain region, leading to significant size and weight restrictions. To overcome this limitation, we have developed a miniature robotic multi-probe neural microdrive that utilizes novel phase-change-material-filled resistive heater micro-grippers. The microscopic dimensions, gentle gripping action, independent electronic actuation control, and high packing density of the grippers allow for micrometer-precision independent positioning of multiple arbitrarily shaped parallel neural electrodes with only a single piezo actuator in an inchworm motor configuration. This multi-probe-single-actuator design allows for significant size and weight reduction, as well as remote control and potential automation of the microdrive. We demonstrate accurate placement of multiple independent recording electrodes into the CA1 region of the rat hippocampus in vivo in acute and chronic settings. Thus, our robotic neural microdrive technology is applicable towards basic neuroscience and clinical studies, as well as other multi-probe or multi-sensor micro-positioning applications. One Sentence SummaryMiniature robotic multi-probe single-actuator microdrive utilizing phase change material based micro-grippers.

bioengineering↗

bioRxiv2020

Canonical goal-selective representations are absent from prefrontal cortex in a spatial working memory task requiring behavioral flexibility

The prefrontal cortex (PFC)s functions are thought to include working memory, as its activity can reflect information that must be temporarily maintained to realize the current goal. We designed a flexible spatial working memory task that required rats to navigate - after distractions and a delay - to multiple possible goal locations from different starting points and via multiple routes. This made the current goal location the key variable to remember, instead of a particular direction or route to the goal. However, across a broad population of PFC neurons, we found no evidence of current-goal-specific memory in any previously reported form - i.e. differences in the rate, sequence, phase or covariance of firing. This suggests such patterns do not hold working memory in the PFC when information must be employed flexibly. Instead, the PFC grouped locations representing behaviorally equivalent task features together, consistent with a role in encoding long-term knowledge of task structure.

neuroscience↗

bioRxiv2020

Enhanced stress tolerance through reduction of G3BP and suppression of stress granules

Stress granules (SG) are membrane-less ribonucleoprotein condensates that form in response to various stress stimuli via phase separation. SG act as a protective mechanism to cope with acute stress, but persistent SG have cytotoxic effects that are associated with several age-related diseases. Here, we demonstrate that the testis-specific protein, MAGE-B2, increases cellular stress tolerance by suppressing SG formation through translational inhibition of the key SG nucleator G3BP. MAGE-B2 reduces G3BP protein levels below the critical concentration for phase separation and suppresses SG initiation. Importantly, knockout of the MAGE-B2 mouse ortholog confers hypersensitivity of the male germline to heat stress in vivo. Thus, MAGE-B2 provides cytoprotection to maintain mammalian spermatogenesis, a highly thermo-sensitive process that must be preserved throughout reproductive life. These results demonstrate a mechanism that allows for tissue-specific resistance against stress through fine-tuning phase separation and could aid in the development of male fertility therapies.

cell biology↗

bioRxiv2019

The statistical structure of the hippocampal code for space as a function of time, context, and value

Hippocampal activity represents many behaviorally important variables, including context, an animals location within a given environmental context, time, and reward. Here we used longitudinal calcium imaging in mice, multiple large virtual environments, and differing reward contingencies to derive a unified probabilistic model of hippocampal CA1 representations centered on a single feature - the field propensity. Each cells propensity governs how many place fields it has per unit space, predicts its reward-related activity, and is preserved across distinct environments and over months. The propensity is broadly distributed--with many low, and some very high, propensity cells --and thus strongly shapes hippocampal representations. The result is a range of spatial codes, from sparse to dense. Propensity varied ~10-fold between adjacent cells in a salt-and-pepper fashion, indicating substantial functional differences within a presumed cell type. The stability of each cells propensity across conditions suggests this fundamental property has anatomical, transcriptional, and/or developmental origins.

neuroscience↗