Pharmacological, neural, and psychological mechanisms underlying psychedelics: A critical review

Neuroscience & Biobehavioral Reviews, Год журнала: 2022, Номер 140, С. 104793 - 104793

Опубликована: Июль 22, 2022

This paper provides a critical review of several possible mechanisms at different levels analysis underlying the effects and therapeutic potential psychedelics. At (1) biochemical level, psychedelics primarily affect 5-HT2A receptor, increase neuroplasticity, offer period for social reward learning, have anti-inflammatory properties. (2) neural been associated with reduced efficacy thalamo-cortical filtering, loosening top-down predictive signaling an increased sensitivity to bottom-up prediction errors, activation claustro-cortical-circuit. (3) psychological shown induce altered affective states, they cognition, belief change, exert effects, can result in lasting changes behavior. We outline unifying account contrast this model pluralistic causation. Ultimately, better understanding specific could allow more targeted approach. highlight current challenges psychedelic research provide agenda foster insight causal-mechanistic pathways therapy.

Язык: Английский

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A transcriptional rheostat couples past activity to future sensory responses

Cell, Год журнала: 2021, Номер 184(26), С. 6326 - 6343.e32

Опубликована: Дек. 1, 2021

Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons then distinguished downstream brain circuits. Here, we show that each of the ∼1,000 olfactory neuron (OSN) subtypes in mouse harbors a distinct transcriptome whose content is precisely determined interactions between its odorant receptor environment. This transcriptional variation systematically organized support adaptation: expression levels more than 70 genes relevant transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust new over hours, accurately predict acute OSN-specific odor responses. The periphery therefore separates salient signals from predictable via rheostat moment-to-moment state reflects past constrains future; these findings suggest general model structured within cell type individual experience.

Язык: Английский

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Development of the mammalian main olfactory bulb

Development, Год журнала: 2022, Номер 149(3)

Опубликована: Фев. 1, 2022

ABSTRACT The mammalian main olfactory bulb is a crucial processing centre for the sense of smell. forms early during development and functional from birth. However, system continues to mature change throughout life as target constitutive adult neurogenesis. Our Review synthesises current knowledge prenatal, postnatal development, focusing on maturation, morphology, functions interactions its diverse constituent glutamatergic GABAergic cell types. We highlight not only great advances in understanding made recent years, but also gaps our present that most urgently require addressing.

Язык: Английский

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α-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease

Journal of Neuroscience, Год журнала: 2023, Номер 43(6), С. 1051 - 1071

Опубликована: Янв. 3, 2023

Parkinson's disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathologic changes in the pathway of transgenic (Tg) mice both sexes expressing human A30P mutant α-synuclein (α-syn; α-syn-Tg mice) at 6–7 and 12–14 months age, representing early late-stages motor progression, respectively. α-Syn-Tg late stages exhibited behavioral deficits, which correlated with severe α-syn pathology projection neurons (PNs) pathway. In parallel, bulb (OB) neurogenesis was reduced OB granule cells six to seven periglomerular months, respectively, could contribute dysfunction. Proteomic analyses showed a disruption endocytic exocytic pathways during appeared exacerbated synaptic terminals when developed deficits months. Our data suggest that (1) recapitulate functional seen PD; (2) structures exhibit spatiotemporal disparities for vulnerability pathology; (3) restricted pathway; (4) adult OB; (5) endocytosis exocytosis defects may further explain deficits. SIGNIFICANCE STATEMENT Olfactory dysfunction characteristic symptom (PD). Using (α-syn)-expressing mouse model, demonstrated appearance disease, accompanied accumulation system. This included reduction as well vesicular transport affecting function, are likely contributing

Язык: Английский

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Sodium channel endocytosis drives axon initial segment plasticity

Science Advances, Год журнала: 2023, Номер 9(37)

Опубликована: Сен. 15, 2023

Activity-dependent plasticity of the axon initial segment (AIS) endows neurons with ability to adapt action potential output changes in network activity. Action initiation at AIS highly depends on clustering voltage-gated sodium channels, but molecular mechanisms regulating their remain largely unknown. Here, we developed genetic tools label endogenous channels and scaffolding protein, reveal nanoscale organization longitudinally image hippocampal slices primary cultures. We find that N -methyl- d -aspartate receptor activation causes both long-term synaptic depression rapid internalization within minutes. The clathrin-mediated endocytosis distal increases threshold for generation. These data a fundamental mechanism activity-dependent reorganization suggests intrinsic excitability shares conserved features plasticity.

Язык: Английский

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Effects of nasal inflammation on the olfactory bulb

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Дек. 9, 2022

Abstract Sinonasal diseases, such as rhinosinusitis, affect up to 12% of individuals each year which constitutes these diseases some the most common medical conditions in world. Exposure environmental pathogens and toxicants via nasal cavity can result a severe inflammatory state commonly observed conditions. It is well understood that epithelial neuronal cells lining olfactory mucosa, including sensory neurons (OSNs), are significantly damaged diseases. Prolonged inflammation may also lead hyposmia or anosmia. Although various agents induce different ways distinct cellular molecular interactions, has similar consequences on structure homeostatic function bulb (OB) first relay center for information brain. Atrophy OB occurs thinning superficial layers nerve layer, glomerular external plexiform layer. Intrabulbar circuits include connectivity between projection neurons, OSNs, interneurons become dysregulated synaptic pruning dendritic retraction take place. Furthermore, glial other immune hyperactivated results upregulated cytokine production. Moreover, many features present case SARS-CoV-2 infection. This review summarizes impact morphological physiological rodent OB.

Язык: Английский

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Aberrant axon initial segment plasticity and intrinsic excitability of ALS hiPSC motor neurons

Cell Reports, Год журнала: 2023, Номер 42(12), С. 113509 - 113509

Опубликована: Ноя. 29, 2023

Dysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes the axon initial segment (AIS), site action potential generation, could impact in ALS human induced pluripotent stem cell (hiPSC) motor neurons. find that early TDP-43 and C9orf72 hiPSC neurons show an increase length AIS impaired activity-dependent plasticity linked abnormal homeostatic regulation activity intrinsic hyperexcitability. In turn, these hyperactive drive increased spontaneous myofiber contractions vitro units. contrast, late postmortem shortening, progress hypoexcitability. At molecular level, aberrant expression master scaffolding protein ankyrin-G AIS-specific voltage-gated sodium channels mirror dynamic function excitability. Our results point toward as important dysfunction

Язык: Английский

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Cell type- and layer-specific plasticity of olfactory bulb interneurons following olfactory sensory neuron ablation

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 1, 2024

Lifelong neurogenesis endows the mouse olfactory system with a capacity for regeneration that is unique in mammalian nervous system. Throughout life, sensory neurons (OSNs) are generated from epithelium (OE) stem cells nose, while subventricular zone generates neuroblasts migrate to bulb (OB) and differentiate into multiple populations of inhibitory interneurons. Methimazole (MMZ) selectively ablates OSNs, but OE enables OSN repopulation gradual recovery input OB within 6 weeks. However, it not known how interneurons affected by this loss subsequent following MMZ treatment. We found dopaminergic neuron density was significantly reduced 7–14 days post-MMZ recovered substantially at 35 days. The parvalbumin-expressing unaffected MMZ; however, their soma size post-MMZ, recovering Surprisingly, we transient increase calretinin-expressing glomerular external plexiform layers, granule cell layer, 7 post-MMZ. This could be accounted increased may result calretinin expression. Together, our data demonstrate type- layer-specific changes interneuron morphology after treatment, providing new insight range plasticity mechanisms employed circuits during input.

Язык: Английский

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Ex vivo functional characterization of mouse olfactory bulb projection neurons reveals a heterogenous continuum

eNeuro, Год журнала: 2025, Номер 12(3), С. ENEURO.0407 - 24.2025

Опубликована: Фев. 4, 2025

Mitral cells (MCs) and tufted (TCs) in the olfactory bulb (OB) act as an input convergence hub transmit information to higher areas. Since first characterized, they have been classed distinct projection neurons based on size location: laminarly arranged MCs with a diameter larger than 20 µm mitral layer (ML) smaller TCs spread across both ML external plexiform layers (EPL). Recent vivo work has shown that these encode complementary information, akin parallel channels other sensory systems. Yet, many ex studies still collapse them into single class, mitral/tufted, when describing their physiological properties impact circuit function. Using immunohistochemistry whole-cell patch-clamp electrophysiology fixed or acute slices from adult mice, we attempted align data test soma size-based classifier of bulbar using passive intrinsic firing properties. We found there is no clear separation between cell types active Rather, heterogeneous continuum three loosely clustered subgroups: EPL, putative ML. These findings illustrate large functional heterogeneity present within OB complement existing literature highlighting how systems preponderant possibly used decode complex information.

Язык: Английский

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Neuroinflammation causes mitral cell dysfunction and olfactory impairment in a multiple sclerosis model

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Март 8, 2025

Язык: Английский

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