Abstract
Certain neuronal populations are selectively vulnerable to alpha-synuclein pathology in Parkinson’s Disease, yet the reasons for this selectivity are unclear. Pathology affects neuronal populations that are anatomically connected although the contribution of neuronal connectivity remains to be quantitatively explored. Herein, we simulate the contribution of the connectome alone to the spread of arbitrary aggregates using a computational model of temporal spread within an abstract representation of the mouse mesoscale connectome. Our simulations are compared with the neuron-to-neuron spread of alpha-synuclein that has been observed with in vivo spreading experiments in rats. We find that neuronal connectivity appears to be compatible with the spreading pattern of alpha-synuclein pathology however, it may be per se insufficient to determine the anatomical pattern of protein spreading observed in experimental animals, suggesting a role of selective vulnerability of neuronal pathways to alpha-synuclein diffusion, accumulation and pathology.
Nomenclature
- AAA
- Anterior amygdalar area
- Allen SDK
- Allen Brain Institute Software Development Kit
- AMB
- Nucleus ambiguus
- AP
- Area postrema
- APN
- Anterior pretectal nucleus
- CEAc
- Central amygdalar nucleus capsular
- DMH
- Dorsomedial nucleus of the hypothalamus
- DMX
- Dorsal motor nucleus of the vagus nerve
- GRN
- Gigantocellular reticular nucleus
- IGX
- Inferior ganglion of the vagus (nodose ganglion)
- IRN
- Intermediate reticular nucleus
- LC
- Locus ceruleus
- LHA
- Lateral hypothalamic area
- MARN
- Magnocellular reticular nucleus
- MDRN
- Medullary reticular nucleus
- MEV
- Midbrain trigeminal nucleus
- MG
- Medial geniculate complex
- MRN
- Midbrain reticular nucleus
- NTS
- Nucleus of the solitary tract
- PAG
- Periaqueductal gray
- PARN
- Parvicellular reticular nucleus
- PB
- Parabrachial nucleus
- PCG
- Pontine central gray
- PD
- Parkinson’s disease
- PG
- Pontine gray
- PP
- Peripeduncular nucleus
- PPN
- Pedunculopontine nucleus
- PRN
- Pontine reticular nucleus
- PSTN
- Parasubthalamic nucleus
- PSV
- Principal sensory nucleus of the trigeminal
- PVH
- Paraventricular hypothalamic nucleus
- RM
- Nucleus raphe magnus
- RN
- Red nucleus
- RO
- Nucleus raphe obscurus
- RPA
- Nucleus raphe pallidus
- RR
- Midbrain reticular nucleus retrorubral area
- SBPV
- Subparaventricular zone
- SC
- Superior colliculus motor related
- SGX
- Superior ganglion of the vagus (jugular ganglion)
- SLC
- Subceruleus nucleus
- SNc
- Substantia nigra pars compacta
- STN
- Subthalamic nucleus
- TRN
- Dorsal tegmental nucleus
- TU
- Tuberal nucleus
- XII
- Hypoglossal nucleus