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Hwaun, E.

Publications and source records attributed to Hwaun, E..

5 recordsLinked to original sources

Topological supramolecular network enabled highly conductive and stretchable organic bioelectronics

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. However, the grand challenge remains for the conducting polymer to possess both high mechanical ductility and good electrical conduction at cellular level feature sizes. This longstanding material limitation in organic bioelectronics has impeded the full exploitation of its unique benefits. Here, we introduce a new molecular engineering strategy based on rationally designed topological supramolecular networks, which allows effective decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We achieve two orders of magnitude improvement in the conductivity under 100% strain in physiological environment, along with the capability for direct photopatterning down to 2 m. These unprecedented capabilities allow us to realize previously inaccessible bioelectronic applications including high-resolution monitoring of soft and malleable creatures, e.g., octopus, and localized neuromodulation down to single nucleus precision for controlling organ-specific activities through delicate tissues, e.g., brainstem.

bioengineering↗

Impairments in Hippocampal Place Cell Sequences during Errors in Spatial Memory

Theta and gamma rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We used a delayed match-to-place memory task to investigate whether such coordination of hippocampal place cell sequences is disrupted when memory errors occur. As rats approached a learned reward location, place cell sequences represented paths extending toward the reward location during correct trials. During error trials, paths coded by place cell sequences were significantly shorter as rats approached incorrect stop locations, with place cell sequences starting at a significantly delayed phase of the theta cycle. During rest, place cell sequences replayed representations of paths that were highly likely to end at the correct reward location during correct but not error trials. The relationship between place cell sequences and gamma rhythms, however, did not differ between correct and error trials. These results suggest that coordination of place cell sequences by theta rhythms and sharp wave-ripples is important for successful spatial memory.

neuroscience↗

Re-expression of SynGAP Protein in Adulthood Improves Translatable Measures of Brain Function and Behavior in a Model of Neurodevelopmental Disorders

BackgroundNeurodevelopmental disorder (NDD) risk genes have pleiotropic biological functions, such as control over both developmental and non-developmental processes that influence disease-related phenotypes. Currently, it remains unclear how developmental versus non-developmental processes influence the duration and/or effectiveness of permissive treatment windows for NDDs. SYNGAP1 haploinsufficiency causes an NDD defined by autistic traits, cognitive impairment, and epilepsy. Syngap1 heterozygosity in mice disrupts a developmental critical period, and, consistent with this, certain behavioral abnormalities are resistant to gene therapy initiated in adulthood. However, the Syngap1 endophenotype is extensive and this protein has diverse cell biological functions. Therefore, SynGAP pleiotropy may influence the permissive treatment window for previously untested disease-relevant phenotypes.\n\nMethodsA whole-body gene restoration technique was used to determine how restoration of SynGAP protein in adult heterozygous mice impacted previously untested phenotypes, such as memory, seizure susceptibility, systems-level cortical hyperexcitability, and hippocampal oscillations linked to mnemonic processes.\n\nResultsAdult restoration of SynGAP protein in haploinsufficient mice reversed long-term contextual memory deficits and behavioral measures of seizure susceptibility. Moreover, SynGAP re-expression in adult mice eliminated brain state-dependent, patient-linked paroxysmal interictal spiking and increased the amplitude of hippocampal theta oscillations.\n\nConclusionsSynGAP protein in the mature brain dynamically regulates neural circuit function and influences disease-relevant phenotypes. The impact of these findings is that treatments targeting certain debilitating aspects of SYNGAP1-related disorders may be effective throughout life. Moreover, the efficacy of experimental treatments for SYNGAP1 patients may be quantifiable through changes in species-conserved, state-dependent pathological electroencephalogram signals.

neuroscience↗

CA3 place cells that represent a novel waking experience are preferentially reactivated during sharp wave-ripples in subsequent sleep

A popular model of memory consolidation posits that recent memories stored in the hippocampus are reactivated during sleep and thereby transferred to neocortex for long-term storage. This process is thought to occur during sharp wave-ripples (SWRs) in non-rapid eye movement (NREM) sleep. But whether the hippocampus consolidates all recent memories in the same manner remains unclear. An efficient memory system may extract novel information from recent experiences for preferential consolidation. In the hippocampus, memories are thought to be stored initially in CA3. Therefore, CA3 place cells that encode novel experiences may be preferentially reactivated during SWRs in subsequent sleep. To test this hypothesis, we recorded CA3 place cells in rats during exposure to a familiar and a novel environment and during subsequent overnight sleep. We found that cells that preferentially coded a novel environment showed larger firing rate increases during SWRs in NREM sleep than cells that preferentially coded a familiar environment. Moreover, CA3 place cell ensembles replayed trajectories from a novel environment during NREM sleep with higher fidelity than trajectories from a familiar environment. Together, these results suggest that CA3 representations of novel experiences are preferentially processed during subsequent sleep.

neuroscience↗

Grid cell co-activity patterns during sleep reflect spatial overlap of grid fields during active behaviors

Continuous attractor network models of grid formation posit that recurrent connectivity between grid cells controls their patterns of co-activation. Grid cells from a common module exhibit stable offsets in their periodic spatial tuning curves across environments, which may reflect recurrent connectivity or correlated sensory inputs. Here we explore whether cell-cell relationships predicted by attractor models persist during sleep states in which spatially informative sensory inputs are absent. We recorded ensembles of grid cells in superficial layers of medial entorhinal cortex during active exploratory behaviors and overnight sleep. Per pair and collectively, we found preserved patterns of spike-time correlations across waking, REM, and non-REM sleep, which reflected the spatial tuning offsets between these cells during active exploration. The preservation of cell-cell relationships across states was not explained by theta oscillations or CA1 activity. These results suggest that recurrent connectivity within the grid cell network drives grid cell activity across behavioral states.

neuroscience↗