Biology subjects

Kim, Y.-c.

Publications and source records attributed to Kim, Y.-c..

4 recordsLinked to original sources

bioRxiv2026

Neuronal ramping and theta power during freely-moving and head-fixed mouse interval timing.

An important paradigm to study executive function is interval timing, which requires participants to estimate a temporal interval, often with a motor response. Interval timing translates from rodents to humans and can model neurodegenerative and neuropsychiatric disease. Interval timing also has parallel, time-dependent neurophysiology in rodents and humans, including time-dependent linear changes in neuronal firing rates over a temporal interval (ramping activity) and low-frequency [~]4 Hz "theta" activity evoked by trial start and response. Despite these translational features, an important confound of interval timing is movement and motor preparation, as participants must report their estimates by planning a movement. To address this confound, we first trained a group of 7 mice in a freely-moving interval timing task in which mice had to move across an operant chamber and nosepoke at the correct time to receive food reward. These mice were then trained in a head-fixed version of interval timing in which mice receive liquid reward for holding still for 3 seconds at the correct location, with reward access randomized to probe interval timing behavior. Despite vastly different motor sequences, we found prominent ramping activity in mouse prefrontal cortex ensembles and prefrontal cortical [~]4 Hz activity evoked both by trial start and preceding the timed decision. These data provide evidence that prefrontal neuronal ramping and theta activity is not linked to a specific motor program but rather a feature of the temporal organization of behavior.

animal behavior and cognition↗

bioRxiv2026

Loss of ASIC1A-dependent inhibitory neuron activity in basolateral amygdala is associated with increased CO2-evoked jumping

BackgroundResponding appropriately to threats is critical for survival. Dysregulated defensive responses are core features of psychiatric illnesses including panic disorder and post-traumatic stress disorder. Carbon dioxide (CO2) inhalation evokes defensive behaviors in both humans and mice. Here we investigated the role of acid-sensing ion channels (ASICs) in CO2-evoked jumping in mice. MethodsDefensive behaviors (jumping and freezing) were assessed in response to CO2 inhalation and basolateral amygdala (BLA) acidification. We tested the role of ASICs using global knockout mice and Asic1aloxP/loxP mice transduced with AAV-CMV-Cre or AAV-CaMKII-Cre in the BLA. Effects of CO2 on single neuron firing and local field potentials were studied via BLA microwire arrays. ResultsASIC1A disruption increased CO2-evoked jumping while reducing freezing, paralleled by increased BLA c-Fos induction. Acidification of the BLA recapitulated these effects. Virus-mediated ASIC1A disruption in BLA did not resolve the locus of ASIC1A action in jumping. CO2 inhalation suppressed firing in most BLA neurons, though a small number increased firing. ASIC1A disruption enhanced CO2-induced suppression of narrow waveform neurons (putative interneurons), and facilitated excitation of wide waveform neurons (putative principal neurons). Additionally, CO2 produced concentration-dependent broadband power suppression with selective theta enhancement, effects that were augmented by ASIC1A disruption. ConclusionsTogether, these findings suggest that ASIC1A promotes interneuron activity during acidosis and that its loss may reduce inhibition of principal neuron output, shifting defensive responses from freezing toward jumping. These results advance our understanding of how brain pH and ASICs regulate defensive behavior, with potential implications for understanding dysregulated defensive responses.

neuroscience↗

bioRxiv2024

Amphetamine increases timing variability by degrading prefrontal ramping activity

BackgroundAmphetamine is a commonly abused psychostimulant that increases synaptic catecholamine levels and impairs executive functions. However, it is unknown how acute amphetamine affects brain areas involved in executive control, such as the prefrontal cortex. We studied this problem in mice using interval timing, which requires participants to estimate an interval of several seconds with a motor response. Rodent prefrontal cortex ensembles are required for interval timing. We tested the hypothesis that amphetamine disrupts interval timing by degrading prefrontal cortex temporal encoding. MethodsWe first quantified the effects of amphetamine on interval timing performance by conducting a meta-analysis of 11 prior rodent studies. We also implanted multielectrode recording arrays in the dorsomedial prefrontal cortex of 7 mice and then examined the effects of 1.5 mg/kg D-amphetamine injected intraperitoneally on interval timing behavior and prefrontal neuronal ensemble activity. ResultsA meta-analysis of previous literature revealed that amphetamine produces a large effect size on interval timing variability across studies but only a medium effect size on central tendencies of interval timing. We found a similar effect on interval timing variability in our task, which was accompanied by greater trial-to-trial variability in prefrontal ramping, attenuated interactions between pairs of ramping neurons, and dampened low-frequency oscillations. ConclusionsThese findings suggest that amphetamine alters prefrontal temporal processing by increasing the variability of prefrontal ramping. Our work provides insight into how amphetamine affects timing-related brain activity, which may be useful in developing new neurophysiological markers for amphetamine use and novel treatments targeting the prefrontal cortex.

neuroscience↗

bioRxiv2024

Generation and validation of a D1 dopamine receptor Flpo knock-in mouse

BackgroundDopamine is a powerful neuromodulator of diverse brain functions, including movement, motivation, reward, and cognition. D1-type dopamine receptors (D1DRs) are the most prevalently expressed dopamine receptors in the brain. Neurons expressing D1DRs are heterogeneous and involve several subpopulations. Studying these neurons has been limited by current animal models, especially when considering their integration with conditional or intersectional genetic tools. New methodTo address this limitation, we developed a novel Drd1-P2A-Flpo (Drd1-Flpo) mouse line in which the Flpo gene was knocked in immediately after the Drd1 gene using CRISPR-Cas9. We validated the Drd1-Flpo line by confirming Flp expression and functionality specific to D1DR+ neurons. Comparison with existing methods: The Drd1-Flpo line is useful resource for studying subpopulation of D1DR+ neurons with intersectional genetic tools. ConclusionsWe demonstrated brain-wide GFP expression driven by Drd1-Flpo, suggesting that this mouse line may be useful for comprehensive anatomical and functional studies in many brain regions. The Drd1-Flpo model will advance the study of dopaminergic signaling by providing a new tool for investigating the diverse roles of D1DR+ neurons and their subpopulations in brain disease. Significance StatementThe roles of dopamine in the brain are mediated by dopamine receptors. D1-type dopamine receptors (D1DRs) and D1DR-expressing (D1DR+) neurons play important roles in various brain functions. We generated a Drd1-Flpo mouse line that expresses Flp recombinase in D1DR+ neurons. This novel Drd1-Flpo mouse facilitates investigation of specific roles of D1DR+ neurons in various brain areas including the striatum, frontal cortex, and cerebellum, and it provides an alternative to existing Drd1-Cre mice. In addition, the Drd1-Flpo mouse line provides a tool for intersectional genetic studies, when used with existing transgenic Cre lines. The Drd1-Flpo mouse line can help unravel the specific contributions of D1DR+ neuron subpopulations to brain function and dysfunction.

neuroscience↗