In vertebrate brains, virtually all neural circuits operate inside a dense matrix of axons (fibers) that have a strongly stochastic character. These fibers originate in the brainstem raphe region, produce highly tortuous trajectories, and release serotonin (5-hydroxytryptamine, 5-HT), with other neurotransmitters. They can robustly regenerate in the adult mammalian brain and appear to support neuroplasticity [1], with implications for mental disorders [2] and artificial neural networks [3]. The self-organization of this “serotonergic” matrix remains poorly understood.
In our previous study, we have shown that serotonergic fibers can be modeled as paths of fractional Brownian motion (FBM), a continuous-time stochastic process. FBM is parametrized by the Hurst index, which defines three distinctive regimes: subdiffusion (H < 0.5), normal diffusion (H = 0.5), and superdiffusion (H > 0.5). In two-dimensional (2D) shapes based on the adult mouse brain, simulated FBM-fibers (with H = 0.8) have produced regional distributions similar to those of the actual serotonergic fibers [4]. However, increments of superdiffusive FBM trajectories have long-range positive correlations, which implies that a fiber path in one 2D-section depends on its history in other sections. In a major extension of this study, we used a supercomputing simulation to generate 960 fibers in a complex, three-dimensional shape based on the late-embryonic mouse brain (at embryonic day 17.5). The fibers were modeled as paths of reflected FBM with H = 0.8. The reflection was caused by natural neuroanatomical borders such as the pia and ventricles. The resultant regional densities were compared to the actual fiber densities in the corresponding neuroanatomically-defined regions, based on a recently published comprehensive map [5]. The relative simulated densities showed strong similarities to the actual densities in the telencephalon, diencephalon, and mesencephalon. The current simulation does not include tissue heterogeneities, but it can be further improved with novel models of multifractional FBM, such as the one introduced by our group [6]. The study demonstrates that serotonergic fiber densities can be strongly influenced by the geometry of the brain, with implications for neurodevelopment, neuroplasticity, and brain evolution.
Acknowledgements:
This research was funded by an NSF-BMBF CRCNS grant (NSF #2112862 to SJ & TV; BMBF #STAXS to RM).
References:
1. Lesch KP, Waider J. Serotonin in the modulation of neural plasticity and networks: implications for neurodevelopmental disorders. Neuron. 2012, 76, 175-191.
2. Daws RE, Timmermann C, Giribaldi B, et al. Increased global integration in the brain after psilocybin therapy for depression. Nat. Med. 2022, 28, 844-851.
3. Lee C, Zhang Z, Janušonis S. Brain serotonergic fibers suggest anomalous diffusion-based dropout in artificial neural networks. Front. Neurosci. 2022, 16, 949934.
4. Janušonis S, Detering N, Metzler R, Vojta T. Serotonergic axons as fractional Brownian motion paths: Insights Into the self-organization of regional densities. Front. Comput. Neurosci. 2020, 14, 56.
5. Awasthi JR, Tamada K, Overton ETN, Takumi T. Comprehensive topographical map of the serotonergic fibers in the male mouse brain. J. Comp. Neurol. 2021, 529, 1391-1429.
6. Wang W, Balcerek M, Burnecki K, et al. Memory-multi-fractional Brownian motion with continuous correlation. arXiv. 2023, 2303.01551.
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Characterizing the diverse cells that associate with the developing commissures of the zebrafish forebrain
During embryonic development of bilaterally symmetrical organisms, neurons send
axons across the midline at specific points to connect the two halves of the nervous
system with a commissure. Little is known about the cells at the midline that
facilitate this tightly regulated process. We exploit the conserved process of vertebrate
embryonic development in the zebrafish model system to elucidate the identity
of cells at the midline that may facilitate postoptic (POC) and anterior commissure
(AC) development. We have discovered that three different gfap+ astroglial cell
morphologies persist in contact with pathfinding axons throughout commissure formation.
Similarly, olig2+ progenitor cells occupy delineated portions of the postoptic
and anterior commissures where they act as multipotent, neural progenitors.
Moreover, we conclude that both gfap+ and olig2+ progenitor cells give rise to neuronal
populations in both the telencephalon and diencephalon; however, these varied
cell populations showed significant developmental timing differences between the
telencephalon and diencephalon. Lastly, we also showed that fli1a+ mesenchymal
cells migrate along the presumptive commissure regions before and during midline
axon crossing. Furthermore, following commissure maturation, specific blood vessels
formed at the midline of the POC and immediately ventral and parallel to the
AC. This comprehensive account of the cellular populations that correlate with the
timing and position of commissural axon pathfinding has supported the conceptual
modeling and identification of the early forebrain architecture that may be necessary
for proper commissure development.
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- NSF-PAR ID:
- 10230029
- Date Published:
- Journal Name:
- Developmental Neurobiology
- Issue:
- 00
- ISSN:
- 1932-8451
- Page Range / eLocation ID:
- 1-25
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/dneu.22801
