Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

eLife, Год журнала: 2024, Номер 13

Опубликована: Апрель 8, 2024

Alzheimer's disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed human animal studies. GABAergic interneurons (INs) within hippocampus coordinate network activity, which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide calretinin play a crucial role. These provide primarily disinhibition principal excitatory (PCs) CA1 region, regulating incoming inputs formation. However, it remains unclear whether AD pathology induces changes activity of I-S3 cells, impacting motifs. Here, using young adult 3xTg-AD mice, we found that while density morphology remain unaffected, there were significant their firing output. Specifically, displayed elongated action potentials decreased rates, was associated with reduced inhibition INs higher recruitment during spatial decision-making object exploration tasks. Furthermore, activation PCs also impacted, signifying early disruptions functionality. findings suggest altered patterns might initiate early-stage dysfunction circuits, potentially influencing progression pathology.

Язык: Английский

---

Unexpected Events Trigger Task-Independent Signaling in VIP and Excitatory Neurons of Mouse Visual Cortex

iScience, Год журнала: 2025, Номер 28(2), С. 111728 - 111728

Опубликована: Янв. 2, 2025

The visual cortex predicts incoming sensory stimuli through internal models that are updated following unexpected events. Cortical inhibitory neurons, particularly vasoactive intestinal polypeptide (VIP) interneurons, play a critical role in representing stimuli. Notably, this response is stimulus non-specific, raising the question of what information it conveys. Given their unique connectivity, we hypothesized during stimuli, VIP neurons encode broad context signals, referred to here as task-independent information. To test hypothesis, analyzed Allen Institute Visual Behavior dataset, which mice viewed repeated familiar images and omissions these images, while two-photon calcium imaging was performed from distinct cell types across primary higher-order areas. Using dimensionality reduction methods, found that, contrast image presentations, trigger signaling excitatory neurons. This may facilitate integration contextual information, enabling predictions.

Язык: Английский

---

Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Cortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following discovery they predominantly function by inhibiting dendritic-targeting somatostatin (SST) disinhibiting PCs. This VIP-SST disinhibitory motif is observed throughout neocortex from mice humans, serves as a key mechanism for top-down (feedback) context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found play an important role in sensory processing, executive functions, attention, sensorimotor integration cortico-cortical thalamocortical feedback interactions. Furthermore, implicated mediating effects reinforcement signals, both reward aversive, via their responsiveness neuromodulators such acetylcholine (ACh), facilitating synaptic plasticity learning. While it evident transcriptomic analyses molecularly heterogeneous group, physiological significance this diversity unclear at present. Here, we characterized functional primary somatosensory cortex leveraging intersectional genetic approaches study IN subtypes. We can be divided into four different populations: group expresses Ca 2+ -binding protein calretinin (CR), two groups express cholecystokinin (CCK), does not either CR or CCK (non-CCK non-CR; nCCK nCR). neurons each exhibit laminar distributions, axonal dendritic arbors, intrinsic electrophysiological properties, efferent connectivity, VIP/CR target almost exclusively SST VIP/nCCK nCR also mainly but connections parvalbumin (PV) INs. These essentially no connectivity (PCs). On hand, VIP/CCK PCs, differ degree which release type modulated endocannabinoids. long-range inputs differentially recruit groups. Intriguingly, find populations subtypes turn, indicating presence specialized subcircuits. Activation subpopulations vivo results differential on network, thus providing evidence modularity actions during

Язык: Английский

---

Optogenetic stimulation of pyramidal neurons in the rat primary visual cortex modulates ON- and OFF- receptive field areas independently

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

In the retina an increase and a decrease in illuminance levels induce ON OFF responses, respectively. This segregation into two major types of visual responses is carried out through lateral geniculate nucleus (LGN) to primary cortex area V1. V1, these are partially merged on single neurons, although domains still found layers II-III with no direct inputs from LGN. However, it unclear whether V1 feedback circuits can process independently. Here, we demonstrate that local optogenetic activation layer IV–VI pyramidal neurons modulates receptive field (RF) Although RF was reduced for both (77.9% 60.7% control, respectively; n = 60), changes did not correlate (Spearman’s rank correlation coefficient ρ 0.144, p > 0.27, 60). contrast, response amplitudes correlated (ρ 0.486, < 0.0003, These results be explained by assuming amplitude largely dependent intrinsic neuronal properties, while modulated loops presynaptically.

Язык: Английский

---

Nitrous oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 3, 2025

Язык: Английский

---