Noncanonical short-latency auditory pathway directly activates deep cortical layers

Introduction

Sensory information reaches the cerebral cortex through multiple ascending pathways, with parallel routes existing even within a single sensory modality^{1, 2, 3, 4, 5, 6–7}. These pathways are thought to extract and transmit different aspects of the sensory environment, though their specific roles remain largely unclear. Characterizing the unique information each pathway conveys and determining how their inputs are spatially and temporally distributed within the cortex is crucial for understanding how the brain ultimately integrates these inputs to create unified sensory perceptions.

In the auditory system, the cortex receives input through two anatomically distinct pathways: the lemniscal and non-lemniscal pathways^8,9. The lemniscal pathway originates in the cochlear nucleus, ascends through the central nucleus of the inferior colliculus (CIC) to the ventral division (MGv) of the medial geniculate nucleus (MGN), and terminates in the primary auditory cortex. This pathway is characterized by auditory-specific, short-latency responses with tonotopic organization and is thus considered the primary ascending route. In contrast, the non-lemniscal pathways follow complementary routes, arising from the external and dorsal cortices of the inferior colliculus (ECIC and DCIC), traveling through the dorsal and medial divisions of the MGN (MGd and MGm), and projecting broadly across auditory cortical areas. Neurons in the non-lemniscal pathways typically exhibit longer-latency responses with broader frequency tuning, receive dense cortical feedback, and often respond to non-auditory stimuli^{8,10, 11, 12, 13, 14, 15–16}. These distinct characteristics have fostered the view that non-lemniscal pathways serve either as conduits from the primary to secondary auditory cortices or as slower, modulatory routes for integrating multisensory signals, rather than as ascending pathways carrying peripheral sound information^{17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28–29}.

At the thalamocortical level, lemniscal projections from MGv to L4 of the primary cortex have been considered the initial entry point for auditory signals. This “canonical cortical circuit” model³⁰ posits that sensory information flows sequentially within the cortical column along the L4 → L2/3 → L5/6 axis before being transmitted to subcortical structures and higher-order cortices^26,27 (Fig. 1a). However, emerging findings suggest the presence of ascending sensory inputs with short latencies directly reaching deeper cortical layers^{31, 32–33} and higher-order auditory cortices^{34, 35, 36, 37, 38, 39–40}, calling into question whether...