THE DEVELOPMENTAL ORIGINS OF MOTOR-SENSORY FEEDBACK CIRCUITRY IN CORTEX

To accurately and efficiently construe the world the brain uses a strategy of comparing external sensory input to internal representations of the environment. These internal representations are provided by top-down inputs to sensory cortices. One example of this is feedback signals from motor cortex that provide a representation of motor output. This motor-sensory feedback circuitry is found in all sensory cortices but, despite this prevalence, it is not known how it is established during development. We hypothesise that these feedback circuits derive from particular progenitor populations during embryonic development.
To investigate this, we used in utero electroporation in mice to label L2/3 pyramidal neurons derived through direct and indirect neurogenesis (dNG and iNG). We performed dual patch-clamp recordings from dNG-derived and iNG-derived neurons in acute slices of S1 with optogenetic activation of inputs from M1 to investigate lineage-specific motor feedback. We then used calcium imaging during locomotion to examine lineage-dependent contributions to motor-sensory feedback circuitry in both S1 and V1.
The patch-clamp recordings revealed that dNG-derived and iNG-derived neurons receive different synaptic inputs from M1, with larger amplitude EPSCs and IPSCs in iNG-derived neurons than in dNG-derived neurons. We then showed that iNG-derived neurons are more strongly modulated by locomotion than dNG-derived neurons, both positively and negatively, and in both S1 and V1.
This work demonstrates that developmental lineage determines the motor feedback to L2/3 pyramidal neurons across both S1 and V1, and reveals a developmental origin for the organisation of motor-sensory feedback circuitry in the mammalian cortex.