Biology subjects

Hyun, J. H.

Publications and source records attributed to Hyun, J. H..

3 recordsLinked to original sources

bioRxiv2023

Serotonin in the orbitofrontal cortex enhances cognitive flexibility

Cognitive flexibility is a brains ability to switch between different rules or action plans depending on the context. However, cellular level understanding of cognitive flexibility have been largely unexplored. We probed a specific serotonergic pathway from dorsal raphe nuclei (DRN) to the orbitofrontal cortex (OFC) while animals are performing reversal learning task. We found that serotonin release from DRN to the OFC promotes reversal learning. A long-range connection between these two brain regions was confirmed anatomically and functionally. We further show that spatiotemporally precise serotonergic action directly enhances the excitability of OFC neurons and offers enhanced spike probability of OFC network. Serotonergic action facilitated the induction of synaptic plasticity by enhancing Ca2+ influx at dendritic spines in the OFC. Thus, our findings suggest that a key signature of flexibility is the formation of choice specific ensembles via serotonin-dependent synaptic plasticity.

neuroscience↗

bioRxiv2021

Tagging active neurons by soma-targeted Cal-Light

Verifying causal effects of neural circuits is essential for proving direct a circuit-behavior relationship. However, techniques for tagging only active neurons with high spatiotemporal precision remain at the beginning stages. Here we developed the soma-targeted Cal-Light (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression. Such modification simultaneously increases the signal-to-noise ratio (SNR) of reporter gene expression and reduces the light requirement for successful labeling. Because of the enhanced efficacy, the ST-Cal-Light enables the tagging of functionally engaged neurons in various forms of behaviors, including context-dependent fear conditioning, leverpressing choice behavior, and social interaction behaviors. We also targeted kainic acid-sensitive neuronal populations in the hippocampus which subsequently suppressed seizure symptoms, suggesting ST-Cal-Lights applicability in controlling disease-related neurons. Furthermore, the generation of a conditional ST-Cal-Light knock-in (KI) mouse provides an opportunity to tag active neurons in a region- or cell-type specific manner via crossing with other Cre-driver lines. Thus, the versatile ST-Cal-Light system links somatic action potentials to behaviors with high temporal precision, and ultimately allows functional circuit dissection at a single cell resolution.

neuroscience↗

bioRxiv2020

Kv1.2 contributes to pattern separation by regulating the hippocampal CA3 neuronal ensemble size

Kv1.2 expression in rodent CA3 pyramidal cells (CA3-PC) is polarized to distal apical dendrites, and regulate the synaptic responses to perforant pathway (PP) inputs. Accordingly, Kv1.2 haploinsufficiency (Kcna2+/-) in CA3-PCs, but not Kv1.1 (Kcna1+/-), lowered the threshold for long-term potentiation at PP-CA3 synapses. The Kcna2+/- mice, but not Kcna1+/-, displayed impairments in contextual fear discrimination task. The size and overlap of CA3 ensembles activated by the first visits to slightly different contexts were not different between wildtype and Kcna2+/- mice, but these ensemble parameters diverged over training days between genotypes, suggesting abnormal plastic changes in the CA3 network of Kcna2+/- mice. Eventually, the Kcna2+/- mice exhibited larger ensemble size and overlap upon retrieval of two contexts, compared to wildtype or Kcna1+/- mice. These results suggest that Kv1.2 subunits prevent promiscuous plastic changes at PP-CA3 synapses, and contribute to sparse representation of memories and pattern separation in the CA3 network.

neuroscience↗