Montero, T. | bioRxiv Science

bioRxiv2026

A VTA-pontine GABA pathway biases backward locomotion via local and distal inhibition

Locomotor direction in mammals is implemented by descending circuits, yet how midbrain selection systems bias directional motor output remains unclear. Here we define a projection-defined inhibitory pathway from the ventral tegmental area to the oral pontine reticular nucleus (VTAPnO) whose activation is sufficient to drive backward locomotion. These TH- VTA neurons form monosynaptic GABAA synapses locally while projecting to PnO, establishing a dual local-projection inhibitory architecture. Somatic activation reliably induced backward locomotion, and selective stimulation of VTAPnO terminals reproduced the effect. Pathway recruitment produced a rapid transient increase in dopaminergic single-unit activity and frequency-dependent increases in dopaminergic population calcium signals in awake mice. During forced locomotion, chronically recorded VTAPnO neurons were preferentially engaged during reverse compared to forward rotations. Together, these findings reveal a projection-defined midbrain pathway that biases locomotor direction through coordinated local inhibition and distal engagement of a brainstem premotor node.

neuroscience↗

bioRxiv2022

Geometrical factors determining dendritic domain intersection between neurons: a modeling study

Overlap between dendritic trees of neighboring neurons is a feature of nervous systems. Overlap allows neurons to share common afferences and defines the topography of the circuit they belong to. Proximity is also a requirement for dendritic communication, including dendro-dendritic synaptic contacts. We simulated overlap dynamics between pairs of ventral tegmental area dopamine neurons, a population characterized by diverse and extensive dendritic domains. Using each neurons 3D convex hull (CH) as a proxy for dendritic domain size and shape, we examined intersection versus cell-to-cell distance curves for 210 pairs of neurons, and found that decay dynamics were diverse and complex, indicating that intersection between real dendritic domains does not comply with spherical or isotropic shape assumptions. We re-examined intersection dynamics for the same 210 pairs, but this time with either: a) a normalized volume corresponding to the average volume of all CHs, b) normalized shapes, using an average CH shape, or CHs from neurons exhibiting average dendritic distribution, isotropy or morphology, or c) a normalized cell body position, which we artificially placed in each CHs centroid. All three interventions significantly increased pair intersection and simplified decay dynamics, yet shape normalization had the strongest influence. Critically, shape uniformity was also the most relevant factor for increased dendritic domain pair intersection using the neurons original brain position and distances. We applied this experimental approach to other populations using reconstructions from neuromorpho.org database and found that shape and intersection dynamics were cell-type dependent. We conclude that intersection between neurons is not only maximized by proximity, but that individual-specific dendritic domain geometries have a profound impact too. The results predict that one biological solution for circuits requiring selective connectivity is to exhibit greater heterogeneity in size, cell body location, and especially shape, among their constituent neuronal elements.

neuroscience↗