Daliparthi, V. | bioRxiv Science

bioRxiv2021

Spinal V1 neurons inhibit motor targets locally and sensory targets distally to coordinate locomotion

Rostro-caudal coordination of spinal motor output is essential for locomotion. Most spinal interneurons project axons longitudinally to govern locomotor output, yet their connectivity along this axis remains unclear. In this study, we use larval zebrafish to map synaptic outputs of a major inhibitory population, V1 (Eng1+) neurons, which are implicated in dual sensory and motor functions. We find that V1 neurons exhibit long axons extending rostrally and exclusively ipsilaterally for an average of 6 spinal segments; however, they do not connect uniformly with their post-synaptic targets along the entire length of their axon. Locally, V1 neurons inhibit motor neurons (both fast and slow) and other premotor targets including V2a, V2b and commissural pre-motor neurons. In contrast, V1 neurons make robust inhibitory contacts throughout the rostral extent of their axonal projections onto a dorsal horn sensory population, the Commissural Primary Ascending neurons (CoPAs). In a computational model of the ipsilateral spinal network, we show that this pattern of short range V1 inhibition to motor and premotor neurons is crucial for coordinated rostro-caudal propagation of the locomotor wave. We conclude that spinal network architecture in the longitudinal axis can vary dramatically, with differentially targeted local and distal connections, yielding important consequences for function.

neuroscience↗

bioRxiv2020

Autism-linked gene FoxP1 selectively regulates the cultural transmission of learned vocalizations

Autism spectrum disorders (ASD) are characterized by impaired learning of culturally transmitted behaviors like social skills, speech, and language1-3. These behaviors are learned by copying parents and other social models during development, a two-stage process that involves forming memories of appropriate behaviors during social experiences and then using those memories to guide imitation. How ASD-linked genes impair these often-intertwined aspects of learning is not known, thereby limiting our understanding of the developmental progression of ASD and the targeting of therapeutic interventions. Here we show that these aspects of learning are dissociable and that the ASD-linked gene FoxP1 selectively impairs learning from social experience, but not behavioral imitation. Haploinsufficiency of FOXP1 in humans causes FOXP1 syndrome, a neurodevelopmental disorder typified by severe disruptions in speech and language development, and other ASD-associated symptoms4,5. We tested how knockdown of FoxP1 (FP1-KD) affects the cultural transmission of vocal behaviors in zebra finches, a songbird that learns by memorizing and vocally copying the song of an adult song-tutor. We find that FP1-KD blocks song learning in juvenile birds by selectively impairing their ability to encode a memory during social experiences with a songtutor. These learning deficits are linked to disruptions in experience-driven structural and functional plasticity. However, if birds are exposed to tutor-song prior to FP1-KD, their ability to imitate that song during development is unaffected. Thus, FP1-KD impairs cultural transmission of vocalizations by disrupting the ability to form appropriate vocal memories, yet spares the ability to use previously acquired memories to guide vocal learning. This indicates that learning from social experience may be particularly vulnerable in FOXP1 syndrome.

neuroscience↗