Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

AbstractDimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional Amerindian medicine (e.g. Ayahuasca) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention. Historical and technical restrictions impaired understanding how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico systems biology analyses support 5-MeO-DMT’s anti-inflammatory effects and reveal a modulation of proteins associated with long-term potentiation, the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. These results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.

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Multiplexed neurochemical transmission emulated using a dual-excitatory synaptic transistor

npj 2D Materials and Applications ◽

10.1038/s41699-021-00205-4 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Mingxue Ma ◽

Yao Ni ◽

Zirong Chi ◽

Wanqing Meng ◽

Haiyang Yu ◽

...

Keyword(s):

Neural Network ◽

Central Nervous System ◽

Nervous System ◽

Long Term Potentiation ◽

Short Term ◽

Term Potentiation ◽

Binary Neural Network ◽

Neuromorphic Systems ◽

Human Brains

AbstractThe ability to emulate multiplexed neurochemical transmission is an important step toward mimicking complex brain activities. Glutamate and dopamine are neurotransmitters that regulate thinking and impulse signals independently or synergistically. However, emulation of such simultaneous neurotransmission is still challenging. Here we report design and fabrication of synaptic transistor that emulates multiplexed neurochemical transmission of glutamate and dopamine. The device can perform glutamate-induced long-term potentiation, dopamine-induced short-term potentiation, or co-release-induced depression under particular stimulus patterns. More importantly, a balanced ternary system that uses our ambipolar synaptic device backtrack input ‘true’, ‘false’ and ‘unknown’ logic signals; this process is more similar to the information processing in human brains than a traditional binary neural network. This work provides new insight for neuromorphic systems to establish new principles to reproduce the complexity of a mammalian central nervous system from simple basic units.

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Long-Term Potentiation in Isolated Dendritic Spines

PLoS ONE ◽

10.1371/journal.pone.0006021 ◽

2009 ◽

Vol 4 (6) ◽

pp. e6021 ◽

Cited By ~ 16

Author(s):

Amadou T. Corera ◽

Guy Doucet ◽

Edward A. Fon

Keyword(s):

Dendritic Spines ◽

Long Term Potentiation ◽

Term Potentiation

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Plasticity in the projection from the anterior thalamic nuclei to the anterior cingulate cortex in the rat in vivo: paired-pulse facilitation, long-term potentiation and short-term depression

Neuroscience ◽

10.1016/s0306-4522(01)00554-1 ◽

2002 ◽

Vol 109 (3) ◽

pp. 401-406 ◽

Cited By ~ 19

Author(s):

C. Gemmell ◽

S.M. O’Mara

Keyword(s):

Anterior Cingulate Cortex ◽

Long Term Potentiation ◽

Anterior Cingulate ◽

Thalamic Nuclei ◽

Short Term ◽

Paired Pulse ◽

Term Potentiation ◽

Anterior Thalamic Nuclei

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Differential modulation of short-term synaptic dynamics by long-term potentiation at mouse hippocampal mossy fibre synapses

The Journal of Physiology ◽

10.1113/jphysiol.2007.143925 ◽

2007 ◽

Vol 585 (3) ◽

pp. 853-865 ◽

Cited By ~ 16

Author(s):

Anja Gundlfinger ◽

Christian Leibold ◽

Katja Gebert ◽

Marion Moisel ◽

Dietmar Schmitz ◽

...

Keyword(s):

Long Term Potentiation ◽

Mossy Fibre ◽

Differential Modulation ◽

Short Term ◽

Term Potentiation ◽

Synaptic Dynamics

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Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

Biological Chemistry ◽

10.1515/hsz-2019-0110 ◽

2019 ◽

Vol 400 (9) ◽

pp. 1129-1139 ◽

Cited By ~ 2

Author(s):

Iryna Hlushchenko ◽

Pirta Hotulainen

Keyword(s):

Synaptic Plasticity ◽

Dendritic Spines ◽

Hippocampal Neurons ◽

Long Term Potentiation ◽

Excitatory Synapses ◽

Signal Molecule ◽

Brain Functions ◽

Dendritic Shaft ◽

Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

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Structural basis of long-term potentiation in single dendritic spines

Nature ◽

10.1038/nature02617 ◽

2004 ◽

Vol 429 (6993) ◽

pp. 761-766 ◽

Cited By ~ 1423

Author(s):

Masanori Matsuzaki ◽

Naoki Honkura ◽

Graham C. R. Ellis-Davies ◽

Haruo Kasai

Keyword(s):

Dendritic Spines ◽

Long Term Potentiation ◽

Structural Basis ◽

Term Potentiation

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Large and Small Dendritic Spines Serve Different Interacting Functions in Hippocampal Synaptic Plasticity and Homeostasis

Neural Plasticity ◽

10.1155/2016/6170509 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Joshua J. W. Paulin ◽

Peter Haslehurst ◽

Alexander D. Fellows ◽

Wenfei Liu ◽

Joshua D. Jackson ◽

...

Keyword(s):

Dendritic Spines ◽

Fluorescent Protein ◽

Long Term Potentiation ◽

Functional Differentiation ◽

Strong Stimulus ◽

Term Potentiation ◽

Original Size ◽

Green Fluorescent ◽

Homeostatic Response

The laying down of memory requires strong stimulation resulting in specific changes in synaptic strength and corresponding changes in size of dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing and shrinking the synapse to prevent damage from too much Ca2+influx. But do all types of dendritic spines serve both of these apparently opposite functions? Using confocal microscopy in organotypic slices from mice expressing green fluorescent protein in hippocampal neurones, the size of individual spines along sections of dendrite has been tracked in response to application of tetraethylammonium. This strong stimulus would be expected to cause both a protective homeostatic response and long-term potentiation. We report separation of these functions, with spines of different sizes reacting differently to the same strong stimulus. The immediate shrinkage of large spines suggests a homeostatic protective response during the period of potential danger. In CA1, long-lasting growth of small spines subsequently occurs consolidating long-term potentiation but only after the large spines return to their original size. In contrast, small spines do not change in dentate gyrus where potentiation does not occur. The separation in time of these changes allows clear functional differentiation of spines of different sizes.

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