Functional specialization of hippocampal somatostatin-expressing interneurons

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(17)

Published: April 19, 2024

Hippocampal somatostatin-expressing ( Sst ) GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single-cell transcriptome analyses have provided a comprehensive -IN subpopulations census, plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach identify access -INs based on transcriptomic features. Four mouse models single or combinatorial Cre- Flp- expression differentiated functionally distinct CA1 hippocampal Sst- INs that largely tiled the morpho-functional parameter space superfamily. Notably, Sst;;Tac1 intersection revealed population bistratified preferentially synapsed onto fast-spiking (FS-INs) were sufficient interrupt their firing. In contrast, Ndnf;;Nkx2-1 identified oriens lacunosum-moleculare predominantly targeted pyramidal neurons, avoiding FS-INs. Overall, our results provide framework translate into discrete subtypes capture diverse specializations -INs.

Language: Английский

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Neocortical somatostatin neuron diversity in cognition and learning

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Transcriptomic cell-type specificity of local cortical circuits

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Complex neocortical functions rely on networks of diverse excitatory and inhibitory neurons. While local connectivity rules between major neuronal subclasses have been established, the specificity connections at level transcriptomic subtypes remains unclear. We introduce single transcriptome assisted rabies tracing (START), a method combining monosynaptic single-nuclei RNA sequencing to identify cell types, providing inputs defined neuron populations. employ START transcriptomically characterize neurons input 5 different layer-specific cortical populations in mouse primary visual cortex (V1). At subclass level, we observe results consistent with findings from prior studies that resolve using antibody staining, transgenic lines, morphological reconstruction. With improved subtype granularity achieved START, demonstrate various subclasses. These establish resolution types.

Language: Английский

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Functional subtypes of synaptic dynamics in mouse and human

Cell Reports, Journal Year: 2024, Volume and Issue: 43(2), P. 113785 - 113785

Published: Feb. 1, 2024

Synapses preferentially respond to particular temporal patterns of activity with a large degree heterogeneity that is informally or tacitly separated into classes. Yet, the precise number and properties such classes are unclear. Do they exist on continuum and, if so, when it appropriate divide functional regions? In dataset glutamatergic cortical connections, we perform model-based characterization infer characteristics functionally distinct subtypes synaptic dynamics. rodent data, find five clusters partially converge transgenic-associated subtypes. Strikingly, application same clustering method in human data infers highly similar clusters, supportive stable clustering. This nuanced dictionary shapes dynamics provides lens basic motifs information transmission brain.

Language: Английский

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Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Differences in Cajal-Retzius cell density and postnatal persistence across cortical areas revealed by a novel intersectional genetic labeling approach

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

ABSTRACT Cajal-Retzius (CR) cells are glutamatergic neurons that transiently populate the most superficial layer of isocortex and allocortex during development, serving an essential role both prenatal early postnatal brain development. Notably, these disappear from cortical areas by day 14, but persist for much longer in hippocampus. We developed a novel intersectional genetic labeling approach CR captures almost all TRP73-positive throughout allocortex. This strategy offers several advantages over previous methods commonly used cell targeting. Here, we applied this new to investigate distribution persistence whole mouse brain, at four different ages. observed initial density rate their disappearance varies substantially across Strikingly, variation death even between adjacent subregions: comparing medial lateral entorhinal cortex, former retains high months contrast latter. Our results present necessary revision phenomenon persistence, showing that, addition hippocampus, other maintain beyond first two weeks.

Language: Английский

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Differential behavioral engagement of inhibitory interneuron subtypes in the zebra finch brain

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 21, 2024

SUMMARY Within the adult rodent hippocampus, opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting local micro-circuits. However, it is unknown if this disinhibitory motif conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition robustly suppressed by hippocampus proper but not primary neocortex mice and nonhuman primates, with spontaneous tone resected human tissue also following a consistent dichotomy. This hippocampal was established early development when PV-INs were found to regulate population activity. Acute opioid-mediated modulation partially occluded morphine pretreatment, implications for effects of on network activity important learning memory. Together, these findings demonstrate exhibit divergence opioid sensitivity brain regions remarkably evolution highlights underappreciated role acting through immature shaping

Language: Английский

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Disorganized Inhibitory Dynamics and Functional Connectivity in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Individuals with the 22q11.2 deletion syndrome, one of strongest genetic risk factors for schizophrenia, demonstrate cognitive impairments including episodic memory dysfunction. Place cell activity excitatory pyramidal neurons in hippocampus supporting are impaired a mouse model ( Df(16)A +/- ). While dynamics under tight inhibitory control by multiple subtypes GABAergic interneurons, previous studies have predominantly focused on single subtype PV-expressing interneurons; there not yet been describing functional relationships between molecularly identified types mice. Here, we examined interneuron subtype-specific dorsal hippocampal area CA1 mice during random foraging and spatial reward learning tasks. Capitalizing 3D acousto-optical deflector two-photon microscopy post hoc immunohistochemical identification, found that exhibit aberrant responses to locations delayed enrichment extinction. interneurons also carry markedly reduced information subtype-dependent manner. We observed task-dependent changes correlation structure coactivity among subtypes, suggesting broadly disorganized microcircuit functionality mutant Overall, identify widespread heterogeneous alterations learning, reflecting flexibility organization microcircuits. Our study provides critical insights into how schizophrenia-risk mutations affect local-circuit interactions diverse navigation.

Language: Английский

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Brief sleep disruption alters synaptic structures among hippocampal and neocortical somatostatin-expressing interneurons

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 23, 2024

Abstract Study objectives Brief sleep loss alters cognition and synaptic structures of principal neurons in hippocampus neocortex. However, while vivo recording bioinformatic data suggest that inhibitory interneurons are more strongly affected by loss, it is unclear how deprivation affect interneurons’ synapses. Disruption the SST+ interneuron population seems to be a critical early sign neuropathology Alzheimer’s dementia, schizophrenia, bipolar disorder - risk developing all three increased habitual loss. We aimed test various brain regions brief disruption. Methods used Brainbow 3.0 label dorsal hippocampus, prefrontal cortex, visual cortex male SST-CRE transgenic mice, then compared labeled after 6-h period ad lib sleep, or gentle handling (SD) starting at lights on. Results Dendritic spine density among both neocortex was altered subregion-specific manner, with overall thin CA1, dramatic increases volume surface area CA3, small but significant changes (primarily decreases) size PFC V1. Conclusions Our connectivity significantly region-specific manner few hours This suggests cell type-specific mechanism which disrupts excitatory-inhibitory balance networks. Significance Statement Changes function somatostatin-expressing (SST+) have been implicated etiology psychiatric neurological disorders behavior affected. Here, we measure effects very experimental on neocortex, for sleep-dependent memory processing. find only six restructures dendritic spines, causing widespread size. These potential dramatically alter across these networks, leading cognitive disruptions commonly associated

Language: Английский

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