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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Opioid modulation of prefrontal cortex cells and circuits

Neuropharmacology, Journal Year: 2024, Volume and Issue: 248, P. 109891 - 109891

Published: Feb. 27, 2024

Several neurochemical systems converge in the prefrontal cortex (PFC) to regulate cognitive and motivated behaviors. A rich network of endogenous opioid peptides receptors spans multiple PFC cell types circuits, this extensive system has emerged as a key substrate underlying reward, motivation, affective behaviors, adaptations stress. Here, we review current evidence for dysregulated cortical signaling pathogenesis psychiatric disorders. We begin by providing an introduction basic anatomy function system, followed discussion exogenous modulation at behavioral, cellular, synaptic level. Finally, highlight therapeutic potential targets treatment disorders, synthesizing clinical reports altered peptide receptor expression activity human patients summarizing new developments opioid-based medications. This article is part Special Issue on "PFC circuit disease relevant models".

Language: Английский

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Loss of mGlu5 receptors in somatostatin-expressing neurons alters negative emotional states

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: April 4, 2024

Abstract Subtype 5 metabotropic glutamate receptors (mGlu ) are known to play an important role in regulating cognitive, social and valence systems. However, it remains largely unknown at which circuits neuronal types mGlu act influence these behavioral domains. Altered tissue- or cell-specific expression function of has been proposed contribute the exacerbation neuropsychiatric disorders. Here, we examined how regulate activity somatostatin-expressing (SST+) neurons, as well their on behavior brain rhythmic activity. Loss SST+ neurons elicited excitatory synaptic dysfunction a region sex-specific manner together with range emotional imbalances including diminished novelty preference, reduced anxiety-like decreased freezing during retrieval fear memories. In addition, absence processing impaired theta frequency oscillatory medial prefrontal cortex ventral hippocampus. These findings reveal critical controlling excitability necessary for negative states.

Language: Английский

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Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: May 7, 2024

GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), neuron dysfunction contributes to disrupted network activity associated neurological symptoms, assumingly cell type-specific manner. This centric study focuses on identifying specific interneuron subpopulations within TSC, emphasizing the unique characteristics of medial ganglionic eminence (MGE)- caudal (CGE)-derived interneurons. Using single-nuclei RNA sequencing TSC patient material, we identify somatostatin-expressing (SST+) as immature subpopulation TSC. The maturation SST+ may undergo an incomplete switch from excitatory inhibitory signaling during development, resulting reduced properties. Notably, this reveals markers immaturity specifically interneurons, including abnormal NKCC1/KCC2 ratio, indicating imbalance chloride homeostasis crucial for postsynaptic consequences well downregulation GABA

Language: Английский

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Feedforward and disinhibitory circuits differentially control activity of cortical somatostatin interneurons during behavioral state transitions

Cell Reports, Journal Year: 2024, Volume and Issue: 43(5), P. 114197 - 114197

Published: May 1, 2024

Interneurons (INs), specifically those in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-INs, are strongly modulated by the behavioral context. Yet, mechanisms which these INs recruited during active states whether their activity is consistent across sensory cortices remain unclear. We now report that mice, locomotor recruits SST-INs primary somatosensory (S1) but not visual (V1) cortex. This diverse engagement of cannot be explained differences VIP-IN function absent presence input, suggesting involvement feedforward pathways. Accordingly, inactivating thalamus, decreasing activity, significantly reduces modulation locomotion. Model simulations suggest can varying ratios VIP- thalamus-driven activity. By integrating with neuromodulation, anticipated to crucial for adapting processing states.

Language: Английский

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