Nascimento, G. | bioRxiv Science

bioRxiv2025

Auditory regulation of hippocampal locomotion circuits by a non-canonical reticular-limbic pathway

The ability to rapidly detect and respond to unexpected auditory stimuli is critical for adaptive behavior, especially during locomotion. Since movement suppresses auditory cortical activity, it remains unclear how salient auditory information influences locomotor circuits. In this work, using in vivo calcium imaging, electrophysiology, chemo- and optogenetics, we investigate the path that relays loud broadband sounds to the dorsal hippocampus (dHPC) and modulates theta oscillations. We demonstrate that noise accelerates theta frequency and decreases its power, effects mediated by entorhinal cortex (EC) and medial septum (MS) inputs while independent of the primary auditory cortex. Activation of dorsal cochlear nucleus (DCN) neurons projecting to the pontine reticular nucleus (PRN) mimics noise-driven hippocampal responses, supporting a brainstem-limbic auditory processing route. Furthermore, noise selectively modulates CA1 pyramidal neuron and interneuron activity, reflecting diverse circuit dynamics. Finally, loud broadband noise stimulus increased theta coherence between the dHPC and the medial prefrontal cortex (mPFC), enhancing interregional synchronization. These results highlight the mechanisms in which the DCN filters behaviorally relevant sounds promoting acoustic motor integration in the hippocampus during locomotion, without direct influence of the auditory cortex.

neuroscience↗

bioRxiv2024

Layer 5 Martinotti cell activation reduces pyramidal cell population plasticity and improves fine motor function

During motor activity and motor learning, pyramidal cells in the motor cortex receive inputs from local interneurons as well as deeper structures. Layer 5 pyramidal cells in the primary motor cortex then feed commands to spinal circuits for motor execution. The genetic ablation of layer 5 Chrna2 Martinotti cells, which selectively target pyramidal tract pyramidal cells, resulted in disturbed fine motor functions. Using calcium imaging combined with chemogenetics, we show that activation of layer 5 Chrna2 Martinotti cells during training increases pyramidal cell tuning, changes responses temporal patterns and decreases assembly reconfiguration, while not affecting motor learning success rates. However, in mice that had already learned a reach-and-grasp (prehension) task, Chrna2 Martinotti cell activation resulted in improved prehension and increased power in low theta and high gamma bands of local field potentials in the motor cortex. This work indicates that activation of Chrna2 Martinotti cells reduces pyramidal cell assembly plasticity during learning, possibly facilitating already acquired motor skills.

neuroscience↗