Biology subjects

Cho, F. S.

Publications and source records attributed to Cho, F. S..

5 recordsLinked to original sources

bioRxiv2025

A Dual Inhibitory Network in the Thalamic Reticular Nucleus Delineated by Pallidal and Intra-Reticular Inhibition

Long described as an inhibitory "guardian of the gateway," the thalamic reticular nucleus (TRN) shapes which thalamic signals reach the cortex during attention, arousal, and sensory processing. However, how the inhibitory wiring within TRN supports this flexible gating--from modality-specific tuning to global control--remains poorly defined. Using cell type-specific optogenetic input mapping and whole-cell patch-clamp recordings in mice, we dissect inhibitory connectivity in TRN from two major GABAergic sources: the TRN itself and the external globus pallidus (GPe). All recorded TRN neurons received inhibition from the GPe, whereas a subset also received intra-TRN inhibition. Intra-TRN inhibition arose predominantly from somatostatin-expressing onto parvalbumin-expressing TRN neurons (SOM[->]PV), revealing subtype-specific connectivity recruited by thalamic excitation to form a feedforward motif. These findings delineate a dual inhibitory architecture: local intra-TRN circuits provide spatially selective inhibition, whereas pallidal inputs deliver diffuse inhibition. These complementary mechanisms may support both modality-specific gating and global state-dependent control of thalamic output. Graphical AbstractThe thalamic reticular nucleus (TRN) integrates two distinct inhibitory motifs. Sparse, dendrite-targeting intra-TRN connections from parvalbumin- and somatostatin-expressing neurons provide structured, feedforward inhibition recruited by thalamocortical (TC) inputs. In parallel, robust and widespread inhibition from Npas1-expressing neurons of the external globus pallidus (GPe) supplies a strong external drive that can coordinate activity across the TRN. Together, these complementary motifs define a dual inhibitory architecture that may shape thalamocortical gating and highlight cellular entry points for therapeutic intervention. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=183 SRC="FIGDIR/small/680571v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@19035b0org.highwire.dtl.DTLVardef@b4f323org.highwire.dtl.DTLVardef@1c68d8eorg.highwire.dtl.DTLVardef@777c15_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Entorhinal cortex represents task-relevant remote locations independent of CA1

Neurons can collectively represent the current sensory experience while an animal is exploring its environment or remote experiences while the animal is immobile. These remote representations can reflect learned associations1-3 and be required for learning4. Neurons in the medial entorhinal cortex (MEC) reflect the animals current location during movement5, but little is known about what MEC neurons collectively represent during immobility. Here, we recorded thousands of neurons in superficial MEC and dorsal CA1 as mice learned to associate two pairs of rewarded locations. We found that during immobility, the MEC neural population frequently represented positions far from the animals location, which we defined as non-local coding. Cells with spatial firing fields at remote locations drove non-local coding, even as cells representing the current position remained active. While MEC non-local coding has been reported during sharp-wave ripples in downstream CA16, we observed non-local coding more often outside of ripples. In fact, CA1 activity was less coordinated with MEC during non-local coding. We further observed that non-local coding was pertinent to the task, as MEC preferentially represented remote task-relevant locations at appropriate times, while rarely representing task-irrelevant locations. Together, this work raises the possibility that MEC non-local coding could strengthen associations between locations independently from CA1.

neuroscience↗

bioRxiv2021

Interleukin-33 coordinates a microglial phagocytic response and limits corticothalamic excitability and seizure susceptibility

Microglia are key remodelers of neuronal synapses during brain development, but the mechanisms that regulate this process and its ultimate impact on neural circuit function are not well defined. We previously identified the IL-1 family cytokine Interleukin-33 (IL-33) as a novel mediator of microglial synapse remodeling. Here we define the phagocytic program induced in microglia in response to IL-33. We find that IL-33 markedly alters the microglial enhancer landscape and exposes AP-1 transcription factor sites that promote target gene expression. We identify the scavenger receptor MARCO and the pattern recognition receptor TLR2 as downstream mediators of IL-33 dependent synapse engulfment. Conditional deletion of IL-33 in the CNS or its receptor on microglia results in increased numbers of excitatory synapses in the corticothalamic circuit and spontaneous epileptiform activity as well as increased seizure susceptibility by early adulthood. These findings define novel mechanisms through which IL-33 coordinates experience-dependent synaptic refinement to restrict hyperexcitability in the developing brain.

neuroscience↗

bioRxiv2020

Complement factor C1q mediates chronic neuron loss and inflammation post-brain injury

While traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of cortical injury that does not directly damage subcortical structures, we found a chronic increase in C1q expression specifically in the corticothalamic circuit. Increased C1q expression co-localized with neuron loss and chronic inflammation, and correlated with altered cortical rhythms. Blocking C1q counteracted most of these outcomes, suggesting that C1q is a disease modifier in TBI. Since the corticothalamic circuit is important for sensory processing, attention, cognition, and sleep, all of which can be impaired by TBI, this circuit could be a new target for treating TBI-related disabilities.

neuroscience↗

bioRxiv2020

Somatostatin-positive neurons in the reticular thalamus modulate gamma rhythms and visual information in mouse V1

Visual perception in natural environments depends on the ability to focus on salient stimuli while ignoring distractions. This kind of selective visual attention is associated with gamma activity in the visual cortex. While the nucleus reticularis thalami (nRT) has been implicated in selective attention, its role in modulating visual perception remains unknown. Here we show that somatostatin-(SOM) but not parvalbumin-expressing (PV) neurons in the nRT preferentially project to visual thalamic nuclei. In freely behaving mice, single-unit and field recordings reveal powerful modulation of both visual information transmission and gamma activity in primary visual cortex (V1), as well as in the dorsal lateral geniculate nucleus (dLGN). These findings pinpoint the SOM neurons in nRT as powerful modulators of the visual information encoding accuracy in V1, and represent a novel circuit through which the nRT can influence representation of visual information.

neuroscience↗