Biology subjects

Seo, M. S.

Publications and source records attributed to Seo, M. S..

5 recordsLinked to original sources

bioRxiv2026

Blockade of Kv3.1 by MK-801, a PCP-Derivative NMDA Receptor Inhibitor: Implications for Models of Schizophrenia

MK-801, a phencyclidine (PCP) derivative also known as dizocilpine, is a potent noncompetitive antagonist of the N-Methyl-D-aspartate receptor (NMDAr). The NMDAr plays a critical role in mediating excitatory synaptic transmission in the central nervous system (CNS) and is important in regulating synaptic plasticity, learning, and memory. MK-801 is known to induce schizophrenia-like phenotypes in animal models by blocking the NMDAr. Several studies have reported that the cognitive impairment associated with schizophrenia is linked to functional defects of ion channels in parvalbumin-positive GABAergic interneurons. Kv3.1 is a voltage-gated K+ (Kv) channel involved in the rapid repolarization of the action potential in neurons; it is richly expressed in parvalbumin-positive GABAergic interneurons and is associated with fast, repetitive spike generation. A decrease of Kv3.1 in the CNS has been reported to be associated with schizophrenia. In the present study, the effect of MK-801 on Kv3.1 was investigated using the whole-cell patch-clamp technique in Chinese hamster ovary (CHO) cells stably expressing Kv3.1. MK-801 caused a concentration-dependent inhibition of Kv3.1, with an IC50 of 10.81 M and a Hill coefficient of 0.89. The blocking potency was stronger at depolarized potentials, indicating a voltage-dependent block. MK-801 also produced a use-dependent block, inducing progressive inhibition with repeated stimulation at increased frequencies (1 Hz and 2 Hz), consistent with a delay in recovery from inactivation of Kv3.1 in the presence of MK-801. In addition, MK-801 induced a hyperpolarizing shift in the voltage dependence of the steady-state inactivation curve of Kv3.1. Taken together, these results indicate that MK-801 blocks Kv3.1 expressed in CHO cells in a concentration-, voltage-, and state-dependent manner. Given the importance of Kv3.1 in parvalbumin-positive, fast-spiking GABAergic interneurons, these findings suggest that MK-801 may alter the firing patterns of these inhibitory neurons, contributing to the onset and symptoms of schizophrenia.

pharmacology and toxicology↗

bioRxiv2026

Spatially unitized associations occupy an intermediate position along the item-to-association continuum in older adults

Older adults show disproportionate impairments in associative memory relative to memory for individual items. Unitization, the process by which discrete elements are encoded as a single integrated representation, has been proposed to mitigate this deficit by reducing reliance on hippocampal binding and shifting processing toward perirhinal cortex-mediated item-based encoding. However, most prior work has not included a single item baseline, leaving unclear whether unitized associations are truly processed like items. Here, we investigated whether spatial proximity supports associative memory in older adults and how this benefit is reflected in medial temporal lobe (MTL) encoding activity. Participants encoded unrelated object pairs presented either proximally (spatially integrated) or distally (spatially separated), alongside a single item condition. Behaviorally, older adults showed better memory for proximal than distal pairs, though performance remained below that of single items. Neurally, MTL activity scaled with associative demand, with hippocampal activity increasing and perirhinal activity decreasing as demand increased. Results further revealed an anterior-posterior MTL dissociation, with proximal pairs sharing neural properties with both single items and distal pairs without uniquely recruiting either. Furthermore, hippocampal patterns reliably distinguished item from associative encoding, and the parahippocampal cortex discriminated all three conditions, indicating that the item-associative structure of the MTL was preserved in aging. Together, these findings suggest that proximal pairs occupy an intermediate position between item and associative representations within an intact MTL architecture, and that spatial proximity benefits associative memory in older adults by partially, but not fully, shifting associative demands toward item-based processing. HighlightsO_LISpatial proximity improved associative memory in older adults. C_LIO_LIHippocampal and PRC activity scaled with associative binding demands. C_LIO_LISpatially unitized associations fell between single items and distal associations in MTL encoding activity. C_LIO_LIMTL item-association functional structure was preserved in older adults. C_LI

neuroscience↗

bioRxiv2026

Neural correlates of successful relational memory in younger and older adults: An activation likelihood estimation meta-analysis

Relational memory, the ability to encode and retrieve associations among multiple elements of an experience, is a core component of episodic memory that shows disproportionate age-related decline. Despite a substantial neuroimaging literature examining relational memory in aging, findings remain heterogeneous, and no quantitative synthesis has been conducted. The present study addressed this gap using Activation Likelihood Estimation (ALE) meta-analyses to characterize the neural correlates of relational memory success during encoding and retrieval in younger and older adults. Separate within-age-group, conjunction, and subtraction analyses were conducted, along with an exploratory analysis examining a general relational memory network across 70 independent studies. During encoding, younger adults showed robust convergence across medial temporal and prefrontal regions, whereas older adults showed more limited convergence. Shared convergence across age groups was observed in the left hippocampus and right inferior temporal gyrus, and direct age-group contrasts revealed greater prefrontal convergence in younger relative to older adults. During retrieval, younger adults showed convergence in posterior default mode and subcortical regions, whereas older adults showed convergence in the left angular gyrus, with no shared convergence observed across age groups. Across all studies, the hippocampus showed the most robust bilateral convergence across age groups and memory phases, underscoring its critical role in relational binding. Together, these findings provide the first quantitative characterization of the neural correlates of relational memory success in aging and highlight stable hippocampal involvement alongside age-related variability in prefrontal and posterior retrieval-related recruitment.

neuroscience↗

bioRxiv2026

Temporal Interference Modulates Medial Temporal and Frontoparietal Activity During Mnemonic Discrimination: A high-resolution whole-brain fMRI investigation

Mnemonic discrimination--the ability to distinguish between existing memories and similar new inputs--supports accurate memory in the face of interference (e.g., remembering where you parked today versus yesterday in the same parking deck). Although hippocampal pattern separation has been emphasized as a key mechanism, recent theoretical frameworks and empirical findings suggest that surrounding medial temporal lobe and cortical regions also contribute by resolving interference. An important source of interference in everyday life is temporal interference: similar events may compete not only because they overlap perceptually, but also because they are separated by intervening experiences (e.g., having to remember your morning parking spot after a full day of work). Here, we investigated how temporal interference impacts mnemonic discrimination and its neural correlates using high-resolution fMRI and a continuous recognition task in which the lag between an items first presentation and its subsequent target or similar lure was systematically manipulated (10, 60, or 140 intervening trials). Behaviorally, increasing lag impaired both mnemonic discrimination and target recognition. At the neural level, lag effects were not observed in hippocampal subfields. Rather, temporal interference modulated activity in extrahippocampal MTL regions including parahippocampal and perirhinal cortex, as well as distributed cortical regions including frontoparietal control areas. Importantly, lag-related modulation was process-specific, with partially dissociable patterns for successful mnemonic discrimination and target recognition. Together, these findings demonstrate that temporal interference engages a distributed MTL-cortical network that supports interference resolution during mnemonic discrimination.

neuroscience↗

bioRxiv2024

The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway

OBJECTIVETofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor widely used to treat T2DM, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine. APPROACH AND RESULTSThe femoral artery quickly separated from the rabbit and fix it to the organ bath chamber. Subsequently, administer an inhibitor that modulates vascular tension in the rings or remove the endothelium to assess its impact on vasodilation. The results showed the concentration-dependent induction of vasodilation by tofogliflozin, a response that remained unchanged following endothelial removal, pretreatment with the nitric oxide synthase (NOS) inhibitor L-NAME, or the inhibition of low- and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) using apamin in combination with TRAM-34. Furthermore, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of tofogliflozin whereas pretreatment with the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide or the large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline did not. Notably, our findings indicated that Kv7.X, rather than Kv1.5 or Kv2.1, is the primary Kv subtype involved in tofogliflozin-induced vasodilation. The vasodilatory effects of tofogliflozin were also significantly inhibited in femoral arterial rings pretreated with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin and cyclopiazonic acid (CPA). Tofogliflozin-induced vasodilation was unaltered in arterial rings exposed to the adenylyl cyclase inhibitor SQ 22536, the protein kinase A (PKA) inhibitor KT 5720, and the protein kinase G (PKG) inhibitor KT 582 whereas it was effectively reduced by the soluble guanylyl cyclase (sGC) inhibitor ODQ. CONCLUSIONSThese findings suggest that tofogliflozin-induced vasodilation is mediated by the activation of the SERCA pump, the sGC/cGMP pathway, and Kv channels, but not the PKA signaling pathway, other K+ channels, or endothelium-dependent mechanisms.

pharmacology and toxicology↗